normal phenotype
• mice are phenotypically normal and do not display alterations of thymus, spleen or lymph nodes, or develop tumors
|
Allele Symbol Allele Name Allele ID |
Cd19+ wild type MGI:2158247 |
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Summary |
165 genotypes
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• mice are phenotypically normal and do not display alterations of thymus, spleen or lymph nodes, or develop tumors
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• serum IgG1 levels are markedly decreased compared to controls 10- and 35- days after immunization with soluble antigen + IFNalpha stimulation
|
• serum IgG2a levels are markedly decreased compared to controls 10- and 35- days after immunization with soluble antigen + IFNalpha stimulation
|
• serum IgG3 levels are markedly decreased compared to controls 10- and 35- days after immunization with soluble antigen + IFNalpha stimulation
|
• serum IgM levels are markedly decreased compared to controls 10- days after immunization with soluble antigen + IFNalpha stimulation
|
• serum IgG1 levels are markedly decreased compared to controls 10- and 35- days after immunization with soluble antigen + IFNalpha stimulation
|
• serum IgG2a levels are markedly decreased compared to controls 10- and 35- days after immunization with soluble antigen + IFNalpha stimulation
|
• serum IgG3 levels are markedly decreased compared to controls 10- and 35- days after immunization with soluble antigen + IFNalpha stimulation
|
• serum IgM levels are markedly decreased compared to controls 10- days after immunization with soluble antigen + IFNalpha stimulation
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• 3- to 8-fold increase in IgM and IgG antibodies for single stranded DNA; however, this is 2- to 3-fold lower than in mice homozygous for Fastm1.1Cgn and mice do not display the increase in double negative T cells or lymphoproliferative disease seen in Faslpr homozygotes
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• after LPS stimulation, splenic B cells show significantly reduced BrdU incorporation relative to wild-type cells
• under in vitro plasma cell (PC) differentiation conditions, proliferation of CFSE-labeled B cells is halted at division 2-4 upon 5 and 20 ug/mL LPS stimulation
|
• however, LPS-induced B cell activation is unaffected, as indicated by normal upregulation of various activation markers
• moreover, expression of master transcription factors essential for PC differentiation is largely normal
• 3 days after stimulation with LPS, isolated splenic B cells show a 50% reduction of in vitro PC differentiation
|
• significant decrease in NP-specific IgG1 antibody-secreting plasma cells in the spleen and bone marrow on day 10 after NP-CGG immunization
• significant decrease in the frequencies of NP-specific IgM and IgG3 antibody-secreting plasma cells in the spleen on day 5 after NP-LPS immunization
• however, the frequencies and numbers of B220+Fas+CD38- germinal center (GC) B cells in spleen are normal on day 10 after NP-CGG immunization
|
• significant decrease in serum levels of NP-specific IgG1 at all time points after NP-CGG immunization
|
• significant decrease in serum levels of NP-specific IgG2b on days 7, 14 and 21 after NP-CGG immunization
|
• significant decrease in serum levels of NP-specific IgG3 at all time points after NP-CGG immunization
• significant decrease in serum levels of NP-specific IgG3 on days 7, 14 and 21 after NP-LPS immunization
|
• slight but significant decrease in serum levels of NP-specific IgM on days 21 and 28, but not on days 7 14, after NP-CGG immunization
• significant decrease in serum levels of NP-specific IgM on days 7, 14 and 21 after NP-LPS immunization
|
• severely compromised T cell-dependent and T cell-independent antibody responses
|
N |
• 6- to 14-week-old mice show normal B cell development in the bone marrow and no significant changes in peripheral B cell populations in spleen relative to wild-type controls
|
• after LPS stimulation, splenic B cells show significantly reduced BrdU incorporation relative to wild-type cells
• under in vitro plasma cell (PC) differentiation conditions, proliferation of CFSE-labeled B cells is halted at division 2-4 upon 5 and 20 ug/mL LPS stimulation
|
• however, LPS-induced B cell activation is unaffected, as indicated by normal upregulation of various activation markers
• moreover, expression of master transcription factors essential for PC differentiation is largely normal
• 3 days after stimulation with LPS, isolated splenic B cells show a 50% reduction of in vitro PC differentiation
|
• significant decrease in NP-specific IgG1 antibody-secreting plasma cells in the spleen and bone marrow on day 10 after NP-CGG immunization
• significant decrease in the frequencies of NP-specific IgM and IgG3 antibody-secreting plasma cells in the spleen on day 5 after NP-LPS immunization
• however, the frequencies and numbers of B220+Fas+CD38- germinal center (GC) B cells in spleen are normal on day 10 after NP-CGG immunization
|
• significant decrease in serum levels of NP-specific IgG1 at all time points after NP-CGG immunization
|
• significant decrease in serum levels of NP-specific IgG2b on days 7, 14 and 21 after NP-CGG immunization
|
• significant decrease in serum levels of NP-specific IgG3 at all time points after NP-CGG immunization
• significant decrease in serum levels of NP-specific IgG3 on days 7, 14 and 21 after NP-LPS immunization
|
• slight but significant decrease in serum levels of NP-specific IgM on days 21 and 28, but not on days 7 14, after NP-CGG immunization
• significant decrease in serum levels of NP-specific IgM on days 7, 14 and 21 after NP-LPS immunization
|
• after LPS stimulation, splenic B cells show significantly reduced BrdU incorporation relative to wild-type cells
• under in vitro plasma cell (PC) differentiation conditions, proliferation of CFSE-labeled B cells is halted at division 2-4 upon 5 and 20 ug/mL LPS stimulation
|
• significant decrease in histone H2B ubiquitination (ubH2B) levels in resting B cells, LPS-stimulated B220+CD138- B cells, and B220lo CD138+ LPS-induced plasma cells
• reduction in ubH2B is correlated with downregulated expression of several metabolism-related genes in LPS-stimulated B cells
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• mice exhibit normal development, distribution and activation of NK T cells
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• 3- to 8-fold increase in IgM and IgG antibodies for single stranded DNA; however, this is 2- to 3-fold lower than in mice homozygous for Fastm1.1Cgn and mice do not display the increase in double negative T cells or lymphoproliferative disease seen in Faslpr homozygotes
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• double deficient B cells do not show abnormalities is lysophospholipid-induced adhesion
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• impaired development past the immature stage
|
• reduced number of B220+ and CD3- B lymphocytes in spleen and peripheral blood
|
• impaired germinal center formation
|
• impaired development past the immature stage
|
• reduced number of B220+ and CD3- B lymphocytes in spleen and peripheral blood
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
A representative tumor in the nose of a Gt(ROSA)26Sortm1(gp80)Eces/Gt(ROSA)26Sor+ Cd19tm1(cre)Cgn/Cd19+ mouse
• in non-immunized and immunized mice starting at 2 to 3 months of age
|
• mice succumb to tumors between 7 and 19 months of age
|
• FAS-induced
|
• in non-immunized and immunized mice starting at 2 to 3 months of age
|
• immunization fails to promote production of class-switched IgG1 unlike in wild-type mice
|
• mice exhibit fewer IgG1+ B cells compared to in wild-type mice
|
• in the spleen with a slight reduction in the splenic B to T cell ratio
|
• in non-immunized and immunized mice
|
• NP-stimulated
|
• NP-stimulated
|
• resting and NP-stimulated
|
• resting and NP-stimulated
|
• resting and NP-stimulated
|
• mice develop tumors in lymphoid tissues including nasopharynx, armpit, and inguinal region
|
• histocytic/dendritic cell sarcoma
|
• FAS-induced
|
• in non-immunized and immunized mice starting at 2 to 3 months of age
|
• immunization fails to promote production of class-switched IgG1 unlike in wild-type mice
|
• mice exhibit fewer IgG1+ B cells compared to in wild-type mice
|
• in the spleen with a slight reduction in the splenic B to T cell ratio
|
• in non-immunized and immunized mice
|
• NP-stimulated
|
• NP-stimulated
|
• resting and NP-stimulated
|
• resting and NP-stimulated
|
• resting and NP-stimulated
|
• FAS-induced
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• median survival of 1 year
|
• about 50% of mice show frank leukemia and/or hepatic involvement
|
• mice develop B cell lymphoma with a median survival of 1 year
• tumors show a CD45+B220+CD19+IgM+CD43+CD5+ immunophenotype
• mice treated with JQEZ5, an S-5'adenosyl-l-methionine (SAM)-competitive pyridinone inhibitor,
for 6 days show completely cleared malignant population from the spleen without depleting normal B cells
|
• tumor-bearing mice show disruption of the splenic architecture
|
• tumor-bearing mice show expansion of abnormal, large lymphoid cells in the white pulp
|
• tumor-bearing mice show disruption of the splenic architecture
|
• tumor-bearing mice show expansion of abnormal, large lymphoid cells in the white pulp
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
B-cell lymphoma | DOID:707 | J:239472 |
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• development of B cell lymphoma with kinetics and tumor immunophenotype nearly identical to heterozygous conditional mutants
|
• lymphadenopathy with an infiltration of abnormal B220lowMac2low B cells
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• susceptibility to LPS, S. aureus, and Listeria monocytoegenes infection and liver injury was not different from wild-type and no differences in serum TNF levels were detected, indicating that B cell derived Tnf does not play a role in toxicity, host defense, or autoimmunity
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• viable and fertile with no discernible B cell abnormalities
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• decrease in antigen specific levels of IgG3
|
• decrease in antigen specific levels of IgM
|
• decrease in antigen specific levels of IgG3
|
• decrease in antigen specific levels of IgM
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• despite Cre mediated deletion in B cells, mice have normal pre-B, pro-B, immature and mature B cell numbers and normal splenic architecture
|
• defect in the ability of LPS stimulated isolated B cells to differentiate into plasma cells
• however, in a small percentage of cells where Cre mediated recombination did not take place plasma cell differentiation is normal
|
• decrease in germinal center B cell and plasma cell numbers 1 week after immunization
• however, by 2 - 3 weeks after immunization antigen specifc antibody titers are similar to controls suggesting strong selection in germinal centers for the few cells that escaped Cre mediated recombination and expression analysis confirms the presence of B cells expressing SLC3A2 in the germinal centers
|
• impaired antibody secretion following LPS stimulation
|
• impaired class switching following LPS stimulation
|
• activated B cells fail to spread after antibody mediated ligation of integrins
|
• minimal proliferation in response to anti-IgM antibody stimulation
• in vivo, B cells carrying the recombined allele fail to proliferate; however, cells that escape Cre mediated recombination do proliferate and go on to form plasma cells
|
• decrease in basal and antigen specific levels of IgG
|
• decrease in antigen specific levels of IgM
• however, basal IgM levels are similar to controls
|
• defect in the ability of LPS stimulated isolated B cells to differentiate into plasma cells
• however, in a small percentage of cells where Cre mediated recombination did not take place plasma cell differentiation is normal
|
• decrease in germinal center B cell and plasma cell numbers 1 week after immunization
• however, by 2 - 3 weeks after immunization antigen specifc antibody titers are similar to controls suggesting strong selection in germinal centers for the few cells that escaped Cre mediated recombination and expression analysis confirms the presence of B cells expressing SLC3A2 in the germinal centers
|
• impaired antibody secretion following LPS stimulation
|
• impaired class switching following LPS stimulation
|
• activated B cells fail to spread after antibody mediated ligation of integrins
|
• minimal proliferation in response to anti-IgM antibody stimulation
• in vivo, B cells carrying the recombined allele fail to proliferate; however, cells that escape Cre mediated recombination do proliferate and go on to form plasma cells
|
• decrease in basal and antigen specific levels of IgG
|
• decrease in antigen specific levels of IgM
• however, basal IgM levels are similar to controls
|
• minimal proliferation in response to anti-IgM antibody stimulation
• in vivo, B cells carrying the recombined allele fail to proliferate; however, cells that escape Cre mediated recombination do proliferate and go on to form plasma cells
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
|
• no somatic hypermutation takes place
|
|
• decreased B220+ cells but cells have a normal maturation phenotype
• decreased numbers involve IgM+ IgDhi
|
|
• CD23+IgM+ follicular cells in the spleen were reduced as were CD40+ cells
|
|
• reduced in numbers although normal numbers of pro B cells are present in bone marrow
|
|
• germinal center formation is impaired
|
|
• impaired proliferative responses, failure of G1/S transition
|
|
• stimulated antibody production is low
• T cell dependent antibody production more affected than T cell independent production
|
|
• no somatic hypermutation takes place
|
|
• decreased B220+ cells but cells have a normal maturation phenotype
• decreased numbers involve IgM+ IgDhi
|
|
• CD23+IgM+ follicular cells in the spleen were reduced as were CD40+ cells
|
|
• reduced in numbers although normal numbers of pro B cells are present in bone marrow
|
|
• germinal center formation is impaired
|
|
• impaired proliferative responses, failure of G1/S transition
|
|
• stimulated antibody production is low
• T cell dependent antibody production more affected than T cell independent production
|
|
• impaired proliferative responses, failure of G1/S transition
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• of follicular II B cells in the spleen
|
• of follicular I and follicular II B cells in the spleen
• of B cells stimulated with LPS, CpG or anti-IgM F(ab)'2 in vivo or in vitro
|
• impaired marginal zone B cell differentiation
|
• reduced number of class switched IgG1 B cells in the Peyer's patch
• almost complete block of class switch to IgA, IgG1, IgG2b and IgG3
|
• in the spleen
|
• in the spleen
|
• increased percent
|
• absence of the marginal zone B cells peripheral to follicles in the spleen
|
• in the spleen
|
• increased percentage in the peritoneal cavity
|
• decreased follicular II B cell compartment and increase in follicular I B cell numbers in the spleen
|
• following immunization with NP-CG antigen
• however, levels in naive mice are normal
|
• following immunization with NP-CG antigen
|
• in naive mice and following immunization with NP-Ficoll
|
• in naive mice and following immunization with NP-Ficoll
• however, levels are normal following immunization with NP-CG antigen
|
• reduced development with reduced number of class switched IgG1 B cells in the Peyer's patch
|
• of follicular II B cells in the spleen
|
• of follicular I and follicular II B cells in the spleen
• of B cells stimulated with LPS, CpG or anti-IgM F(ab)'2 in vivo or in vitro
|
• of follicular II B cells in the spleen
|
• of follicular I and follicular II B cells in the spleen
• of B cells stimulated with LPS, CpG or anti-IgM F(ab)'2 in vivo or in vitro
|
• impaired marginal zone B cell differentiation
|
• reduced number of class switched IgG1 B cells in the Peyer's patch
• almost complete block of class switch to IgA, IgG1, IgG2b and IgG3
|
• in the spleen
|
• in the spleen
|
• increased percent
|
• absence of the marginal zone B cells peripheral to follicles in the spleen
|
• in the spleen
|
• increased percentage in the peritoneal cavity
|
• decreased follicular II B cell compartment and increase in follicular I B cell numbers in the spleen
|
• following immunization with NP-CG antigen
• however, levels in naive mice are normal
|
• following immunization with NP-CG antigen
|
• in naive mice and following immunization with NP-Ficoll
|
• in naive mice and following immunization with NP-Ficoll
• however, levels are normal following immunization with NP-CG antigen
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• B cell development and antibody secretion are normal
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• in the bone marrow
|
• in the spleen and lymph nodes
|
• in mesenteric lymph nodes and Peyer's patches
|
• in the spleen and lymph nodes
|
• in unstimulated and NP-CG-stimulated mice
|
• in unstimulated and NP-CG-stimulated mice
|
• in the bone marrow
|
• in the spleen and lymph nodes
|
• in mesenteric lymph nodes and Peyer's patches
|
• in the spleen and lymph nodes
|
• in unstimulated and NP-CG-stimulated mice
|
• in unstimulated and NP-CG-stimulated mice
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• B cell precursors are released into the peripheral blood and reduced in the spleen unlike in wild-type mice but not as severely as in Cxcr4tm1Yzo homozygotes
|
• B cell precursors are released into the peripheral blood and reduced in the spleen unlike in wild-type mice but not as severely as in Cxcr4tm1Yzo homozygotes
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• cells treated with PARP-inhibition exhibit increased chromosomal damage compared with cells from Brca2tm1Brn/Brca2tm1Brn Cd19tm1(cre)Cgn/Cd19tm1(cre)Cgn mice
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• cells treated with PARP-inhibition exhibit increased chromosomal damage compared with untreated cells
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
Enlarged spleen and solid organ infiltration with abnormally proliferating T cells in Gt(ROSA)26Sortm1(ITK/SYK)Jrld/Gt(ROSA)26Sor+ Cd19tm1(cre)Cgn/Cd19+ mice
• mice develop lethal wasting and die by 60 weeks of age unlike wild-type mice
|
• mice develop infiltrating lymphocytes into multiple organs unlike in wild-type mice
• lymphomas consists of enlarged, activated, and highly proliferative T cells
|
• at 50 weeks
|
• lymphomas consists of enlarged, activated, and highly proliferative T cells
|
• lymphomas consists of enlarged, activated, and highly proliferative T cells
|
• mice develop infiltrating lymphocytes into multiple organs unlike in wild-type mice
• lymphomas consists of enlarged, activated, and highly proliferative T cells
|
• at 50 weeks
|
• mice develop infiltrating lymphocytes into multiple organs unlike in wild-type mice
• lymphomas consists of enlarged, activated, and highly proliferative T cells
|
• at 50 weeks
|
• lymphomas consists of enlarged, activated, and highly proliferative T cells
|
• lymphomas consists of enlarged, activated, and highly proliferative T cells
|
• mice develop infiltrating lymphocytes into multiple organs unlike in wild-type mice
• lymphomas consists of enlarged, activated, and highly proliferative T cells
|
• lymphomas consists of enlarged, activated, and highly proliferative T cells
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• susceptibility to Citrobacter rodentium infection is similar to wild-type controls
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• susceptibility to Citrobacter rodentium infection is similar to wild-type controls
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• all die by P6
|
• blastoid cells that infiltrate solid organs are seen indicating high-grade lymphoma
• blastoid B cells express low levels of IL7 or CD25 indicating the disease does not resemble acute B-cell lineage leukemia
|
• B cells in the spleen and bone marrow are CD138+ B220int or CD138+ B220low indicating these consist of plasmablasts and plasma cells
|
• B cells in the spleen and bone marrow are CD138+ B220int or CD138+ B220low indicating these consist of plasmablasts and plasma cells
|
• spleens contain homogenous populations of large cells with prominent nucleoli and high proliferation indices
|
• massive
|
• high proliferation indices
|
• recombined B cells exhibit an activated phenotype with high CD80 and Sca-1 expression and elevated CD43 levels
|
• B cells proliferate vigorously in the absence of any specific B cell survival or mitogenic factors for at least 10 days in culture
• high proliferation indices in the spleen
|
• massive reduction in the B220+ IgM- compartment in the bone marrow indicating infiltration by peripheral blastoid B cells
|
• B cells in the spleen and bone marrow are CD138+ B220int or CD138+ B220low indicating these consist of plasmablasts and plasma cells
|
• B cells in the spleen and bone marrow are CD138+ B220int or CD138+ B220low indicating these consist of plasmablasts and plasma cells
|
• spleens contain homogenous populations of large cells with prominent nucleoli and high proliferation indices
|
• massive
|
• high proliferation indices
|
• recombined B cells exhibit an activated phenotype with high CD80 and Sca-1 expression and elevated CD43 levels
|
• B cells proliferate vigorously in the absence of any specific B cell survival or mitogenic factors for at least 10 days in culture
• high proliferation indices in the spleen
|
• B cells proliferate vigorously in the absence of any specific B cell survival or mitogenic factors for at least 10 days in culture
• high proliferation indices in the spleen
|
• massive
|
• high proliferation indices
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
diffuse large B-cell lymphoma | DOID:0050745 | J:228288 |
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• modest reduction in B1 cells (~10%) in peritoneal cavity is seen
|
• reduction in percentage of marginal zone B cells is observed
|
• spleen cell number is increased ~30% compared to wild-type
|
• in response to LPS and dsRNA, B cells have decreased proliferative response
• cells stimulated through Tlr9 or antigen receptor show similar proliferation and apoptosis to wild-type cells
|
• mice mount an inferior IgM response to LPS immunization
|
• in response to LPS and dsRNA, B cells have decreased proliferative response
• cells stimulated through Tlr9 or antigen receptor show similar proliferation and apoptosis to wild-type cells
|
• modest reduction in B1 cells (~10%) in peritoneal cavity is seen
|
• reduction in percentage of marginal zone B cells is observed
|
• spleen cell number is increased ~30% compared to wild-type
|
• mice mount an inferior IgM response to LPS immunization
|
• cells treated with LPS or dsRNA show decreased survival (increased apoptosis) compared to controls at 24 hours, with decreased viability starting at 12 hours
• cells stimulated through Tlr9 or antigen receptor show similar proliferation and apoptosis to wild-type cells
|
• in response to LPS and dsRNA, B cells have decreased proliferative response
• cells stimulated through Tlr9 or antigen receptor show similar proliferation and apoptosis to wild-type cells
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• increased B cell numbers are observed after immunization with anti-IgD antibody compared to immunized controls
|
• plasma cell numbers are 2-fold larger than controls seven days after infection with MCMV
|
• are observed after immunization with anti-IgD antibody compared to immunized controls
|
• increased myeloid numbers are observed after immunization with anti-IgD antibody compared to immunized controls
|
• MCMV-specific CD8 + T cell numbers are about twice as numerous as controls 7 days after infection with MCMV
|
• IL-10 levels are half that of wild-type controls when immunized with anti-IgD antibodies
|
• IL-10 levels are half that of wild-type controls when immunized with anti-IgD antibodies
|
• increased B cell numbers are observed after immunization with anti-IgD antibody compared to immunized controls
|
• plasma cell numbers are 2-fold larger than controls seven days after infection with MCMV
|
• are observed after immunization with anti-IgD antibody compared to immunized controls
|
• increased myeloid numbers are observed after immunization with anti-IgD antibody compared to immunized controls
|
• MCMV-specific CD8 + T cell numbers are about twice as numerous as controls 7 days after infection with MCMV
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• overall reduction of CD19+ B cells in bone marrow
|
• reduced surface expression of IgM in cells from the spleen, lymph nodes, bone marrow and blood
• surface expression of IgD is not affected
|
• CD19+ IgM+ CD5+ peritoneal B cells are decreased in number
|
• in spite of normal follicular architecture
|
• overall reduction of CD19+ B cells in bone marrow
|
• CD19+ IgM+ CD5+ peritoneal B cells are decreased in number
|
• in spite of normal follicular architecture
|
• reduced surface expression of IgM in cells from the spleen, lymph nodes, bone marrow and blood
• surface expression of IgD is not affected
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• absence of Bcl10 expression rescues the early lethality seen in mutant mice wild-type for Bcl10
|
N |
• absence of Bcl10 expression rescues the pathological B-cell activation, differentiation, and malignant proliferation seen in mutant mice wild-type for Bcl10
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• absence of Malt1 expression rescues the early lethality seen in mutant mice wild-type for Malt1
|
N |
• absence of Malt1 expression rescues the pathological B-cell activation, differentiation, and malignant proliferation seen in mutant mice wild-type for Malt1
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• B cell but not T cell numbers are reduced in the bone marrow and spleen to 65% and 50% of control, respectively
• B cell turn over is also increased in double mutants
|
• B cell but not T cell numbers are reduced in the bone marrow and spleen to 65% and 50% of control, respectively
• B cell turn over is also increased in double mutants
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• B cell precursors are found in the blood
• a large number of the B cell precursors die before they can complete the differentiation process
|
• the total number of mature B cells in the spleen is reduced to about 65% of wild-type
|
• the peritoneal B1 cell population is reduced in young and old mutants
|
• the peritoneal B2 cell population is reduced only in older mutants
|
• a greater than 20-fold reduction in the number of T cell independent antigen-specific plasma cells in the bone marrow is seen after immunization with Ficoll
• the number of antibody-secreting cells is reduced in the bone marrow and increased in the spleen 9 days after immunization, however long-term antibody production is not impaired
|
• basal levels of serum IG of all isotypes are reduced
|
• B cell precursors are found in the blood
• a large number of the B cell precursors die before they can complete the differentiation process
|
• the total number of mature B cells in the spleen is reduced to about 65% of wild-type
|
• the peritoneal B1 cell population is reduced in young and old mutants
|
• the peritoneal B2 cell population is reduced only in older mutants
|
• a greater than 20-fold reduction in the number of T cell independent antigen-specific plasma cells in the bone marrow is seen after immunization with Ficoll
• the number of antibody-secreting cells is reduced in the bone marrow and increased in the spleen 9 days after immunization, however long-term antibody production is not impaired
|
• basal levels of serum IG of all isotypes are reduced
|
• B cell follicles are more dispersed, frequently occur deep in the lamina propria, and some have enlarged T cell zones
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• mice exhibit normal adult hematopoiesis
|
N |
• mice exhibit normal B cell and T cell development
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• unlike in Pten deficient mice, B1 B cell numbers are normal in the spleen and peritoneum
|
• defects in class switch recombination associated with Pten deficiency are partially reversed
|
• mice exhibit an increase in marginal zone B cells that is not as great as in Pten null mice but more than in wild-type mice
|
• defects in class switch recombination associated with Pten deficiency are partially reversed
|
• mice exhibit an increase in marginal zone B cells that is not as great as in Pten null mice but more than in wild-type mice
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• 70% of mice die by 20 months
|
• mice develop B cell clonal lymphoproliferations, chronic lymphocytic leukemia , small cell lymphomas, and CD5- non-Hodgkin lymphomas
|
• mice exhibit lymphoproliferation in the peripheral blood (IgM+CD5+B220lo) with characteristics of chronic lymphocytic leukemia
• 25% of mice develop clonal lymphoproliferations
|
• IgM+CD5+B220lo
|
• mice exhibit lymphoproliferation in the peripheral blood (IgM+CD5+B220lo) with characteristics of chronic lymphocytic leukemia
• 25% of mice develop clonal lymphoproliferations
|
• IgM+CD5+B220lo
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
chronic lymphocytic leukemia | DOID:1040 |
OMIM:109543 OMIM:151400 OMIM:609630 OMIM:612557 OMIM:612558 OMIM:612559 |
J:179879 |
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• mice develop B cell clonal lymphoproliferations, chronic lymphocytic leukemia , small cell lymphomas, and CD5- non-Hodgkin lymphomas
|
• mice exhibit lymphoproliferation in the peripheral blood (IgM+CD5+B220lo) with characteristics of chronic lymphocytic leukemia
• 67% of mice develop clonal lymphoproliferations
|
• IgM+CD5+B220lo
|
• mice exhibit lymphoproliferation in the peripheral blood (IgM+CD5+B220lo) with characteristics of chronic lymphocytic leukemia
• 67% of mice develop clonal lymphoproliferations
|
• IgM+CD5+B220lo
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
chronic lymphocytic leukemia | DOID:1040 |
OMIM:109543 OMIM:151400 OMIM:609630 OMIM:612557 OMIM:612558 OMIM:612559 |
J:179879 |
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• mice develop B cell clonal lymphoproliferations, chronic lymphocytic leukemia , small cell lymphomas, and CD5- non-Hodgkin lymphomas
|
• mice exhibit lymphoproliferation in the peripheral blood (IgM+CD5+B220lo) with characteristics of chronic lymphocytic leukemia
• 42% of mice develop clonal lymphoproliferations
|
• IgM+CD5+B220lo
|
• mice exhibit lymphoproliferation in the peripheral blood (IgM+CD5+B220lo) with characteristics of chronic lymphocytic leukemia
• 42% of mice develop clonal lymphoproliferations
|
• IgM+CD5+B220lo
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
chronic lymphocytic leukemia | DOID:1040 |
OMIM:109543 OMIM:151400 OMIM:609630 OMIM:612557 OMIM:612558 OMIM:612559 |
J:179879 |
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• monoclonal B cell lymphocytosis in some mice at 15 - 18 months of age
|
• at 15-18 months increased clonal population in the peripheral blood
|
• expansion or accumulation of small lymphocytes, with a pattern similar small cell lymphocytic leukemia (SLL) or B cell chronic lymphocytic leukemia (CLL) and with characteristic 'smudge' cells in some mice
|
• monoclonal B cell lymphocytosis in some mice at 15 - 18 months of age
|
• at 15-18 months increased clonal population in the peripheral blood
|
• expansion or accumulation of small lymphocytes, with a pattern similar small cell lymphocytic leukemia (SLL) or B cell chronic lymphocytic leukemia (CLL) and with characteristic 'smudge' cells in some mice
|
• a fraction of mice have histological features of small cell lymphocytic leukemia (SLL) or B cell chronic lymphocytic leukemia (CLL)
|
• some of the CD5 negative tumors showed a mature B cell phenotype histologically reminiscent of human diffuse large B cell lymphoma, non-Hodgkin lymphoma
• a minority of CD5 negative tumors showed plasmacytic features similar to lymphoplasmacytic
lymphoma
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
chronic lymphocytic leukemia | DOID:1040 |
OMIM:109543 OMIM:151400 OMIM:609630 OMIM:612557 OMIM:612558 OMIM:612559 |
J:156946 |
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• fraction of mice have histological features of small cell lymphocytic leukemia (SLL) or B cell chronic lymphocytic leukemia (CLL)
|
• some of the CD5 negative tumors showed a mature B cell phenotype histologically reminiscent of human diffuse large B cell lymphoma, non-Hodgkin lymphoma
• a minority of CD5 negative tumors showed plasmacytic features similar to lymphoplasmacytic
lymphoma
|
• monoclonal B cell lymphocytosis in some mice at 15 - 18 months of age
|
• at 15-18 months increased clonal population in the peripheral blood
|
• expansion or accumulation of small lymphocytes, with a pattern similar small cell lymphocytic leukemia (SLL) or B cell chronic lymphocytic leukemia (CLL) and with characteristic 'smudge' cells in some mice
|
• monoclonal B cell lymphocytosis in some mice at 15 - 18 months of age
|
• at 15-18 months increased clonal population in the peripheral blood
|
• expansion or accumulation of small lymphocytes, with a pattern similar small cell lymphocytic leukemia (SLL) or B cell chronic lymphocytic leukemia (CLL) and with characteristic 'smudge' cells in some mice
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• following immunization a severe decrease in the number of antigen-specific IgM secreting cells is seen compared to wild-type mice
• a larger increase in CD138-B220+NP+ B cells expressing GL7 is seen at 7 and 14 days after immunization
|
• the development of both short-lived and post-germinal center long-lived plasma cells is blocked in mutants
|
• pre-plasma memory B-cells are reduced by 75% in the spleen and 95% in the bone marrow, and CD138-B220+NP+ cells comprise the majority of memory B cells
|
• antibody stimulating cell development is completely inhibited in cultures of stimulated B cells, however stimulation of B cells with LPS or LPS and IL-4 results in increased class switch recombination
(J:114881)
|
• very few CD138+B220+/- plasma cells are seen at any time before or after immunization
• 5 days after re-challenge a 99% reduction in CD138+ B220+/- NP+ plasma cells is seen
|
• more numerous germinal centers are seen after immunization
|
• larger germinal centers are seen after immunization
|
• serum Ig levels are reduced in unimmunized mice
|
• in mice immunized with NP-Ficoll serum IgG1 and IgG2a levels are significantly lower in mutants compared to wild-type mice and mutant mice fail to secrete Ig in a recall response
|
• in mice immunized with NP-Ficoll serum IgM levels are significantly lower in mutants compared to wild-type mice and homozygous mice fail to secrete Ig in a recall response
|
• following immunization a severe decrease in the number of antigen-specific IgM secreting cells is seen compared to wild-type mice
• a larger increase in CD138-B220+NP+ B cells expressing GL7 is seen at 7 and 14 days after immunization
|
• the development of both short-lived and post-germinal center long-lived plasma cells is blocked in mutants
|
• pre-plasma memory B-cells are reduced by 75% in the spleen and 95% in the bone marrow, and CD138-B220+NP+ cells comprise the majority of memory B cells
|
• antibody stimulating cell development is completely inhibited in cultures of stimulated B cells, however stimulation of B cells with LPS or LPS and IL-4 results in increased class switch recombination
(J:114881)
|
• very few CD138+B220+/- plasma cells are seen at any time before or after immunization
• 5 days after re-challenge a 99% reduction in CD138+ B220+/- NP+ plasma cells is seen
|
• more numerous germinal centers are seen after immunization
|
• larger germinal centers are seen after immunization
|
• serum Ig levels are reduced in unimmunized mice
|
• in mice immunized with NP-Ficoll serum IgG1 and IgG2a levels are significantly lower in mutants compared to wild-type mice and mutant mice fail to secrete Ig in a recall response
|
• in mice immunized with NP-Ficoll serum IgM levels are significantly lower in mutants compared to wild-type mice and homozygous mice fail to secrete Ig in a recall response
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• 4-fold increase in the number of CD43+IgM- Pro-B cells
|
• relative number of CD21highCD23low marginal zone B cells is decreased
|
• increase in the number of B cells at all stages of development in the bone marrow and spleen
|
• a 3-5 fold increase in the numbers of transitional B cells
|
• an increase in B-2 cell number, but not B-1 cells, from the peritoneal cavity
|
• an increase in CD21intCD23high follicular B cells
|
• a 4-fold increase in the number of IgM+ immature B cells
|
• B cells are highly resistant to multiple cell death stimuli, including cytokine withdrawal, BCR crosslinking, steroid treatment, and DNA damage
• cell cycle progression of splenic B cells is impaired after stimulation with mitogens LPS and anti-IgM, but not CpG-DNA
|
• all isotypes were 5-10 times higher than controls
|
• increased IgG1, IgG2, IgG2b and IgG3
|
• 4-fold increase in the number of CD43+IgM- Pro-B cells
|
• 2-fold increase in total cellularity of bone marrow cells, due to accumulation of developing B cells
|
• relative number of CD21highCD23low marginal zone B cells is decreased
|
• increase in the number of B cells at all stages of development in the bone marrow and spleen
|
• a 3-5 fold increase in the numbers of transitional B cells
|
• an increase in B-2 cell number, but not B-1 cells, from the peritoneal cavity
|
• an increase in CD21intCD23high follicular B cells
|
• a 4-fold increase in the number of IgM+ immature B cells
|
• B cells are highly resistant to multiple cell death stimuli, including cytokine withdrawal, BCR crosslinking, steroid treatment, and DNA damage
• cell cycle progression of splenic B cells is impaired after stimulation with mitogens LPS and anti-IgM, but not CpG-DNA
|
• all isotypes were 5-10 times higher than controls
|
• increased IgG1, IgG2, IgG2b and IgG3
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• LPS-stimulated lymph node B cells exhibit a low frequency of and a delay in increased cell size relative to wild-type cells
|
• IgG class switching is decreased
|
• short-lived IgM-B220lo and IgM+B220lo immature B cells are slightly lower in number
|
• there is a 3-fold reduction in the number of long-lived mature B cells
• mice lack recirculating IgM+IgD+B220hi cells in the bone marrow
|
• short-lived IgM-B220lo B cells are slightly lower in number
|
• total immunoglobin is reduced 3-fold compared to control mice
|
• IgG levels are decreased ranging from a 9.4-fold decrease of IgG1 to a 2-fold decrease in IgG3 levels
|
• LPS-stimulated lymph node B cells exhibit a low frequency of and a delay in increased cell size relative to wild-type cells
|
• IgG class switching is decreased
|
• short-lived IgM-B220lo and IgM+B220lo immature B cells are slightly lower in number
|
• there is a 3-fold reduction in the number of long-lived mature B cells
• mice lack recirculating IgM+IgD+B220hi cells in the bone marrow
|
• short-lived IgM-B220lo B cells are slightly lower in number
|
• total immunoglobin is reduced 3-fold compared to control mice
|
• IgG levels are decreased ranging from a 9.4-fold decrease of IgG1 to a 2-fold decrease in IgG3 levels
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• mice exhibit normal numbers of bone marrow pre-B cells, immature B cells and splenic mature B cells
• mice exhibit normal survival, proliferation and maturation of restricted progenitors
|
N |
• mice exhibit normal numbers of bone marrow pre-B cells, immature B cells and splenic mature B cells
• mice exhibit normal survival, proliferation and maturation of restricted progenitors
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• occasionally
|
• most tumors resemble diffuse large B cell lymphomas (in 6 of 9 mice)
|
• in 3 of 9 mice
|
• occasionally
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• decrease in IgG1-producing cells in bone marrow from unimmunized mice; these cells may represent either plasma cells or memory B cells
|
• decrease in serum levels of secreted IgM, IgG1, IgA and all other IgG isotypes is found in naive mice as compared to controls
|
• decrease in IgG1-producing cells in bone marrow from unimmunized mice; these cells may represent either plasma cells or memory B cells
|
• decrease in serum levels of secreted IgM, IgG1, IgA and all other IgG isotypes is found in naive mice as compared to controls
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• following antigen challenge (NP-Ficoll or NP-KLH) fewer T1 and T2 type B cells are observed in spleen
|
• following antigen challenge (NP-Ficoll or NP-KLH) fewer T1 and T2 type B cells are observed in spleen
|
• following antigen challenge (NP-Ficoll or NP-KLH) fewer T3 cells are observed in spleen
|
• following antigen challenge (NP-Ficoll or NP-KLH) percentage of immature B cells in bone marrow is increased as compared to control
|
• following antigen challenge (NP-Ficoll or NP-KLH)
|
• decrease in IgG1-producing cells in bone marrow from unimmunized mice; these cells may represent either plasma cells or memory B cells
|
• 4 fold decrease in LPS-treated B220loCD138+ splenic B cells
• decline in CD138+ cells in immunized mice
|
• following antigen challenge (NP-Ficoll or NP-KLH) percentage of recirculating B cells in bone marrow is increased as compared to control
|
• following antigen challenge (NP-Ficoll or NP-KLH)
|
• 2 fold decrease in serum levels of secreted IgM, IgG1, IgA and all other IgG isotopes is found in naive mice as compared to controls
|
• specific antibody responses are impaired for both T cell dependent and independent antigens
• mice immunized with NP-Ficoll exhibit less anti-NP antibody of the IgM, IgG2b and IgG3 isotypes
• mice immunized with NP-KLH exhibit less anti-NP antibody of the IgM, IgG1, IgG2c and IgG3 isotopes
• following restimulation, recall response is less than controls
|
• following antigen challenge (NP-Ficoll or NP-KLH) fewer T1 and T2 type B cells are observed in spleen
|
• following antigen challenge (NP-Ficoll or NP-KLH) fewer T1 and T2 type B cells are observed in spleen
|
• following antigen challenge (NP-Ficoll or NP-KLH) fewer T3 cells are observed in spleen
|
• following antigen challenge (NP-Ficoll or NP-KLH) percentage of immature B cells in bone marrow is increased as compared to control
|
• following antigen challenge (NP-Ficoll or NP-KLH)
|
• decrease in IgG1-producing cells in bone marrow from unimmunized mice; these cells may represent either plasma cells or memory B cells
|
• 4 fold decrease in LPS-treated B220loCD138+ splenic B cells
• decline in CD138+ cells in immunized mice
|
• following antigen challenge (NP-Ficoll or NP-KLH) percentage of recirculating B cells in bone marrow is increased as compared to control
|
• following antigen challenge (NP-Ficoll or NP-KLH)
|
• 2 fold decrease in serum levels of secreted IgM, IgG1, IgA and all other IgG isotopes is found in naive mice as compared to controls
|
• ER found in LPS-treated B220loCD138+ cells is dilated and fragmented
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• there is about a 4-fold increase in the number of follicular B cells found in the spleen compared to controls
|
• there are greatly increased numbers of marginal zone B cells in both spleen and lymph nodes
|
• there is about a 4-fold increase in the number of follicular B cells found in the spleen compared to controls
|
• there are greatly increased numbers of marginal zone B cells in both spleen and lymph nodes
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• occasionally
|
• most tumors resemble diffuse large B cell lymphomas (in 6 of 9 mice)
|
• in 3 of 9 mice
|
• occasionally
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• mice do not develop colitis unlike Itgavtm2Hyn Itgavtm2.1Hyn Tg(Tek-cre)1Ywa mice
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• mice exhibit normally differentiating T, B, and myeloid cells
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• mutants exhibit a hunched posture by 4 months of age
|
• mutants exhibit weight loss by 4 months of age
|
• mutants exhibit splenomegaly by 4 months of age
|
• mutants exhibit splenomegaly by 4 months of age
|
• CD19+ B cells are larger than B cells from wild-type mice
• B cell neoplasia
|
• reduction in the frequency of B cells in asymptomatic double mutant mice as compared to controls or either single mutant mouse
|
• mutants older than 6 months of age have a 3-fold increase in the percentage of recirculating B cells in the blood, concurrent with onset of disease
|
• tissues containing the expanded B cell population also display an expansion of CD11b+ myeloid cells
|
• spleens of mutants over 6 months of age exhibit an expansion of CD19+ B cells, resulting in enlarged white pulp areas that often infiltrate and compress the red pulp
|
• B cells exhibit enhanced survival
|
• B cells proliferate to the prosurvival factor B cell activating factor (BAFF) while wild-type B cells do not
• B cells show a more robust proliferative response to LPS or anti-CD40 than wild-type mice
|
• mutants exhibit splenomegaly by 4 months of age
|
• CD19+ B cells are larger than B cells from wild-type mice
• B cell neoplasia
|
• reduction in the frequency of B cells in asymptomatic double mutant mice as compared to controls or either single mutant mouse
|
• mutants older than 6 months of age have a 3-fold increase in the percentage of recirculating B cells in the blood, concurrent with onset of disease
|
• tissues containing the expanded B cell population also display an expansion of CD11b+ myeloid cells
|
• spleens of mutants over 6 months of age exhibit an expansion of CD19+ B cells, resulting in enlarged white pulp areas that often infiltrate and compress the red pulp
|
• B cells exhibit enhanced survival
|
• B cells proliferate to the prosurvival factor B cell activating factor (BAFF) while wild-type B cells do not
• B cells show a more robust proliferative response to LPS or anti-CD40 than wild-type mice
|
• mutants exhibit ruffled fur by 4 months of age
|
• severe morbidity and death occurs in all mutants by 1 year of age
|
• mutants develop marginal zone lymphoma, and less frequently, follicular B cell lymphoma or centroblastic lymphoma
|
• mutants develop spontaneous and lethal mature B cell neoplasms consistent with marginal zone lymphoma
|
• lymphoma infiltrates are seen in nonlymphoid tissues, including liver, lung, heart, and kidney
|
• B cells proliferate to the prosurvival factor B cell activating factor (BAFF) while wild-type B cells do not
• B cells show a more robust proliferative response to LPS or anti-CD40 than wild-type mice
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
B-cell lymphoma | DOID:707 | J:166155 |
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• bone marrow cultured with IL-7 over a 6 day period to promote selective expansion of pre-B cells exhibits an approximate 7-fold enhancement in the frequency of activated immature mutant B cells relative to immature wild-type B cells
• gating on activated B cells shows that immature mutant B cells proliferate to a much greater extent than immature wild-type B cells
• these experiments show that upon BCR engagement, immature B cells are activated and proliferate rather than being inhibited and undergoing anergy
|
• increase in the absolute number of splenic B cells, attributed mainly to the expansion/accumulation of MZ B cells
|
• expansion of the B1 cell population
|
• expansion of the MZ B cell compartment
|
• increase in numbers of IgMhi antibody secreting cells and decrease in numbers of IgGhi antibody secreting cells
|
• reduction in germinal center formation in response to sheep red blood cell immunization and in response to environmental antigens
|
• B cells are responsive to chemotactic stimuli but show reduced directed movement toward the stimulus
|
• cultured B cells show increased apoptosis
|
• B cells are hyperproliferative in response to mitogenic stimuli and exhibit a lower threshold for activation through the B cell antigen receptor
(J:83213)
• B cells exhibit altered cell cycle progression, with an increase in the percentage of cells in S and G2-M stages
(J:83213)
• neonatal B cells proliferate strongly in response to both LPS and anti-IgM F(ab')2 unlike wild-type B cells which show a modest proliferation in response to LPS and no proliferation in response to the anti-IgM F(ab')2
(J:155314)
|
• impaired class-switch recombination in antibody secreting cells in response to a T-dependent antigen; B cells fail to undergo class-switch recombination to IgG3 or IgG1 in the presence of LPS or LPS plus IL-4, respectively
• however, well-formed germinal centers are observed in spleen after immunization
|
• decrease in IgG after TNP-OVA immunization
|
• increase in IgM after TNP-OVA immunization
|
• bone marrow cultured with IL-7 over a 6 day period to promote selective expansion of pre-B cells exhibits an approximate 7-fold enhancement in the frequency of activated immature mutant B cells relative to immature wild-type B cells
• gating on activated B cells shows that immature mutant B cells proliferate to a much greater extent than immature wild-type B cells
• these experiments show that upon BCR engagement, immature B cells are activated and proliferate rather than being inhibited and undergoing anergy
|
• increase in the absolute number of splenic B cells, attributed mainly to the expansion/accumulation of MZ B cells
|
• expansion of the B1 cell population
|
• expansion of the MZ B cell compartment
|
• increase in numbers of IgMhi antibody secreting cells and decrease in numbers of IgGhi antibody secreting cells
|
• reduction in germinal center formation in response to sheep red blood cell immunization and in response to environmental antigens
|
• B cells are responsive to chemotactic stimuli but show reduced directed movement toward the stimulus
|
• cultured B cells show increased apoptosis
|
• B cells are hyperproliferative in response to mitogenic stimuli and exhibit a lower threshold for activation through the B cell antigen receptor
(J:83213)
• B cells exhibit altered cell cycle progression, with an increase in the percentage of cells in S and G2-M stages
(J:83213)
• neonatal B cells proliferate strongly in response to both LPS and anti-IgM F(ab')2 unlike wild-type B cells which show a modest proliferation in response to LPS and no proliferation in response to the anti-IgM F(ab')2
(J:155314)
|
• impaired class-switch recombination in antibody secreting cells in response to a T-dependent antigen; B cells fail to undergo class-switch recombination to IgG3 or IgG1 in the presence of LPS or LPS plus IL-4, respectively
• however, well-formed germinal centers are observed in spleen after immunization
|
• decrease in IgG after TNP-OVA immunization
|
• increase in IgM after TNP-OVA immunization
|
• cultured B cells show increased apoptosis
|
• B cells are hyperproliferative in response to mitogenic stimuli and exhibit a lower threshold for activation through the B cell antigen receptor
(J:83213)
• B cells exhibit altered cell cycle progression, with an increase in the percentage of cells in S and G2-M stages
(J:83213)
• neonatal B cells proliferate strongly in response to both LPS and anti-IgM F(ab')2 unlike wild-type B cells which show a modest proliferation in response to LPS and no proliferation in response to the anti-IgM F(ab')2
(J:155314)
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• B lineage cells were normal in bone marrow, spleen, and lymph nodes
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• failed tolerance induction resulting in abundant autoantibody production, indicating that B cells are prevented from acquiring an anergic state
• B cells have about 10 fold lower bound HEL than in mutants with intact Pten, suggesting that receptor occupancy is reduced on mutant autoreactive B cells and that less HEL is available in adults for inducing and sustaining anergy
• increasing the concentration of free self-antigen confers an anergic phenotype on mutant B cells, but they remain long-lived
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• B cells exhibit normal class switching and microhomology at Smu-Sgamma1 junctions
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• the number of chromosomal aberrations (chromatid breaks, chromosome breaks and radial chromosomes) in B lymphocytes is increased by treatment with KU0058949 (PARP inhibitor) compared to in wild-type mice
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• mice exhibit normal B cell numbers and lymph node size
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• cells treated with PARP-inhibition exhibit increased chromosomal damage compared with wild-type cells
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• chromosomal damage induced by PARP-inhibition is rescued compared to in cells from Brca1tm2Cxd/Brca1tm2Cxd Cd19tm1(cre)Cgn/Cd19+ mice
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• increased switching to a small extent compared with Trp53bp1tm1Jc homozygotes
|
• increased switching to a small extent compared with Trp53bp1tm1Jc homozygotes
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• impaired proliferation response to stimulation; cells do not undergo activation
|
• impaired proliferation response to stimulation; cells do not undergo activation
|
• impaired proliferation response to stimulation; cells do not undergo activation
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• B cell lymphoblastic leukemia/lymphoma in 4 of 9 mice
|
• B cell lymphoblastic leukemia/lymphoma in 4 of 9 mice
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• slightly in vivo
• in vitro without stimulation and after stimulation with anti-CD40 antibodies or LPS
|
• B cell development in the spleen is altered
• however, mice exhibit normal B cell development in the bone marrow
|
• in the spleen
|
• in the spleen
|
• in re-circulating B cells
• slightly in the spleen
|
• in the peritoneal cavity
|
• in the peritoneal cavity
|
• 5 times
|
• doubled in the spleen
|
• diminished in size
|
• after NP-CGG stimulation with diminished NP-specific IgM and IgG1
|
• enlarged in size
|
• 7 times
|
• diminished NP-specific IgM and IgG1 after NP-CGG stimulation
|
• after NP-Ficoll stimulation
|
• diminished NP-specific IgM and IgG1 after NP-CGG stimulation
|
• enlarged in response to anti-CD40 antibodies and IL4
|
• slightly in vivo
• in vitro without stimulation and after stimulation with anti-CD40 antibodies or LPS
|
• B cell development in the spleen is altered
• however, mice exhibit normal B cell development in the bone marrow
|
• in the spleen
|
• in the spleen
|
• in re-circulating B cells
• slightly in the spleen
|
• in the peritoneal cavity
|
• in the peritoneal cavity
|
• 5 times
|
• doubled in the spleen
|
• diminished in size
|
• after NP-CGG stimulation with diminished NP-specific IgM and IgG1
|
• enlarged in size
|
• 7 times
|
• diminished NP-specific IgM and IgG1 after NP-CGG stimulation
|
• after NP-Ficoll stimulation
|
• diminished NP-specific IgM and IgG1 after NP-CGG stimulation
|
• enlarged in response to anti-CD40 antibodies and IL4
|
• slightly in vivo
• in vitro without stimulation and after stimulation with anti-CD40 antibodies or LPS
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• B cell numbers are increased in adult spleen and lymph nodes
• the number of T2 transitional, follicular and marginal zone B cells is increased in the spleen
|
• the number of T2 transitional B cells is increased in the spleen
• the number of T1 transitional B cells in slightly increased (1.4-fold)
|
• the percent and number of marginal zone B cells is increased
|
• in adult mice
|
• adult mice have splenomegaly
|
• spontaneous germinal centers form
|
• white pulp is enlarged
|
• adult mice have an increased in the size and number of lymphoid follicles
|
• adult mice have enlarged lymph nodes
|
• when challenged with TNP-Ficoll, mice generate higher titers of TNO-specific IgM, igG1, IgG2a, IgG2b, and IgG3 compared to wild-type mice
• when challenged with T dependent antigen (TNP-KLH), mice only show an increase in TNP-specific IgM response
• the T-I antibody response in increased while the T-D IgG1 response is normal
|
• unstimulated ex vivo B cell survive longer than for wild-type B cells with 30% of B cells alive after 16 days in culture when control cells were no longer alive
• B cell activating factor did not enhance ex vivo survival
• B cell do not undergo apoptosis ex vivo as wild-type B cells do
|
• serum IgA is elevated 2- to 5-fold
|
• germinal center B cells express more surface IgG
• serum IgG2a, IgG2b and IgG3 are elevated 2- to 5-fold
|
• germinal center B cells express more surface IgM
• serum IgM is elevated 2- to 5-fold
|
• mice display autoimmune manifestations such as double stranded DNA antibodies and the presence of lymphocyte infiltrate in the kidney and liver
|
• in 80% of mice
|
• mice do not exhibit a reduction in spleen weight or depletion of B cells in response to administration of TACI-Ig (an inhibitor or B cell activating factor and a proliferation-inducing ligand)
|
• 3 of 4 mice contain lymphocyte infiltration at multiple locations in the kidney and liver
|
• 3 of 4 mice contain lymphocyte infiltration at multiple locations in the kidney and liver
|
• unstimulated ex vivo B cell survive longer than for wild-type B cells with 30% of B cells alive after 16 days in culture when control cells were no longer alive
• B cell activating factor did not enhance ex vivo survival
• B cell do not undergo apoptosis ex vivo as wild-type B cells do
|
• adult mice have splenomegaly
|
• B cell numbers are increased in adult spleen and lymph nodes
• the number of T2 transitional, follicular and marginal zone B cells is increased in the spleen
|
• the number of T2 transitional B cells is increased in the spleen
• the number of T1 transitional B cells in slightly increased (1.4-fold)
|
• the percent and number of marginal zone B cells is increased
|
• in adult mice
|
• spontaneous germinal centers form
|
• white pulp is enlarged
|
• serum IgA is elevated 2- to 5-fold
|
• germinal center B cells express more surface IgG
• serum IgG2a, IgG2b and IgG3 are elevated 2- to 5-fold
|
• germinal center B cells express more surface IgM
• serum IgM is elevated 2- to 5-fold
|
• unstimulated ex vivo B cell survive longer than for wild-type B cells with 30% of B cells alive after 16 days in culture when control cells were no longer alive
• B cell activating factor did not enhance ex vivo survival
• B cell do not undergo apoptosis ex vivo as wild-type B cells do
|
• adult mice have splenomegaly
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• striking increase in B cell size coincident with the presence of large and irregular multilobulated nuclei indicating severe segregation defects
|
• acute loss of B cells that is not seen in either single conditional mutant
|
• increase in spontaneous sister chromatid exchange levels in B cells
|
• increase in spontaneous sister chromatid exchange levels in B cells
|
• striking increase in B cell size coincident with the presence of large and irregular multilobulated nuclei indicating severe segregation defects
|
• acute loss of B cells that is not seen in either single conditional mutant
|
• increase in spontaneous sister chromatid exchange levels in B cells
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• mice exhibit normal myeloid, T lymphoid and B lymphoid lineages and cell cycle of lineage progenitors
|
N |
• mice exhibit normal myeloid, T lymphoid and B lymphoid lineages and cell cycle of lineage progenitors
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• impaired
|
• reduced
|
• reduced TACI+CD138+B220-CD19int early cells and TACI+CD138+B220-CD19- mature cells in the spleen, lymph nodes and bone marrow
• reduced LPS-induced TACI+CD138+B220-CD19int early plasma cells and TACI+CD138+B220-CD19- mature plasma cells
• decreased sheep red blood cell induced IgG1-, Ig2b-, IgG2c-, and IgG3 expressing plasma cells
|
• decreased TACI+CD138+B220intCD19int cells
• decreased plasmablasts in LPS-treated mice
• decreased sheep red blood cell induced IgG1-, Ig2b-, IgG2c-, and IgG3 expressing plasmablasts
|
• mice treated with NP-Ficoll and NP-KLH exhibit reduced NP-specific IgM, IgG, IgG1, IgG2b, IgG2c, IgG3, IgA, and IgE antibodies
|
• at baseline
|
• at baseline
|
• at baseline or mice treated with sheep red blood cells
|
• at baseline and in LPS- or sheep red blood cell-treated mice
|
• at baseline and in LPS- or sheep red blood cell-treated mice
|
• at baseline and in LPS- or sheep red blood cell-treated mice
|
• at baseline and in LPS- or sheep red blood cell-treated mice
|
• at baseline and in LPS- or sheep red blood cell-treated mice
|
• in mice treated with pristane compared with similarly treated control mice
|
• in mice treated with pristane that is not as high as in control mice
|
• in mice treated with pristane that is not as high as in control mice
|
• mice treated with hydrocarbon oil 2, 6, 10, 14-tetramethylpentadecane (TMPD or pristane) to induce systemic lupus erythematosus exhibit reduced increase in autoantibody levels and proteinuria compared with control mice
|
• impaired
|
• reduced
|
• reduced TACI+CD138+B220-CD19int early cells and TACI+CD138+B220-CD19- mature cells in the spleen, lymph nodes and bone marrow
• reduced LPS-induced TACI+CD138+B220-CD19int early plasma cells and TACI+CD138+B220-CD19- mature plasma cells
• decreased sheep red blood cell induced IgG1-, Ig2b-, IgG2c-, and IgG3 expressing plasma cells
|
• decreased TACI+CD138+B220intCD19int cells
• decreased plasmablasts in LPS-treated mice
• decreased sheep red blood cell induced IgG1-, Ig2b-, IgG2c-, and IgG3 expressing plasmablasts
|
• at baseline
|
• at baseline
|
• at baseline or mice treated with sheep red blood cells
|
• at baseline and in LPS- or sheep red blood cell-treated mice
|
• at baseline and in LPS- or sheep red blood cell-treated mice
|
• at baseline and in LPS- or sheep red blood cell-treated mice
|
• at baseline and in LPS- or sheep red blood cell-treated mice
|
• at baseline and in LPS- or sheep red blood cell-treated mice
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• mice exhibit reduced increase in autoantibody levels and proteinuria levels compared with control mice
|
• compared with Faslpr homozygotes
|
• not as severe as in Faslpr homozygotes
|
• not as severe as in Faslpr homozygotes
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• development blocked at the T1 stage
|
• diminished splenic T1 and T2 cells
|
• peritoneal B cells (B1) also reduced
|
• diminished recirculating follicular B cells
|
• splenic marginal B cells were reduced
|
• development blocked at the T1 stage
|
• diminished splenic T1 and T2 cells
|
• peritoneal B cells (B1) also reduced
|
• diminished recirculating follicular B cells
|
• splenic marginal B cells were reduced
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• unlike mice with recombination in T cells, mice do not develop inflammatory bowel disease
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• increased apoptosis at pro-B cell stage
|
• arrested at pro-B cell stage
|
• decrease in peripheral B cells
• 88% reduction of splenic B cells relative to controls
• near absence of lymph node B cells
• detected peripheral B cells did not undergo cre-mediated recombination
|
• increased apoptosis at pro-B cell stage
|
• arrested at pro-B cell stage
|
• decrease in peripheral B cells
• 88% reduction of splenic B cells relative to controls
• near absence of lymph node B cells
• detected peripheral B cells did not undergo cre-mediated recombination
|
• increased apoptosis at pro-B cell stage
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• mice exhibit normal B cell development in the bone marrow and spleen
|
• following with activation LPS, less so when activated with LPS plus IL4
|
• following activated with LPS and IL4, mice exhibit decreased IgG1+ cells, indicating reduced class switch recombination, compared with wild-type mice
|
• following immunization with NP-CGG in alum, splenic B cells exhibit reduced mutation frequency in the rearranged Vh186.2 H chains compared with wild-type cells
• Peyer's patch B cells exhibit reduced accumulation of mutation at the intron downstream of rearranged V genes compared with wild-type cells
|
• following with activation LPS, less so when activated with LPS plus IL4
|
• following activated with LPS and IL4, mice exhibit decreased IgG1+ cells, indicating reduced class switch recombination, compared with wild-type mice
|
• following immunization with NP-CGG in alum, splenic B cells exhibit reduced mutation frequency in the rearranged Vh186.2 H chains compared with wild-type cells
• Peyer's patch B cells exhibit reduced accumulation of mutation at the intron downstream of rearranged V genes compared with wild-type cells
|
• following with activation LPS, less so when activated with LPS plus IL4
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• marginal zone B cell numbers are strongly reduced compared to controls
|
• lysophospholipid-induced induced adhesion is completely abrogated in marginal zone mutant B cells and is reduced in follicular B cells
• lysophospholipid-induced induced LFA-1 (integrin) clustering is abolished in mutant B cells
|
• marginal zone B cell numbers are strongly reduced compared to controls
|
• lysophospholipid-induced induced adhesion is completely abrogated in marginal zone mutant B cells and is reduced in follicular B cells
• lysophospholipid-induced induced LFA-1 (integrin) clustering is abolished in mutant B cells
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• there is only a mild effect on B cell numbers
|
• there is only a mild effect on B cell numbers
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• IgA expressing plasma cells are virtually absent from the spleen and bone marrow of mutants
|
• a 3 fold increase in leukocyte numbers is seen
|
• increased proliferation of mature splenic B cells is seen, however a decrease in B-1 cell proliferation and increase in B-1 cell survival time are also seen
|
• more activated B cells are found in mutants
• sera from 9 week or 8 month old mutants shows increased binding to double stranded DNA indicating impaired control of B cell activation
|
• serum IgA levels are reduced by about 10 fold and are not increased in response to antigens
|
• serum levels of all IgG subclasses are increased with IgG1 showing the largest increase (16 fold)
• IgG3 antigen-induced expression is greatly increased
|
• serum IgM levels and IgM expression by peripheral B cells are increased
|
• IgA expressing plasma cells are virtually absent from the spleen and bone marrow of mutants
|
• a 3 fold increase in leukocyte numbers is seen
|
• increased proliferation of mature splenic B cells is seen, however a decrease in B-1 cell proliferation and increase in B-1 cell survival time are also seen
|
• more activated B cells are found in mutants
• sera from 9 week or 8 month old mutants shows increased binding to double stranded DNA indicating impaired control of B cell activation
|
• serum IgA levels are reduced by about 10 fold and are not increased in response to antigens
|
• serum levels of all IgG subclasses are increased with IgG1 showing the largest increase (16 fold)
• IgG3 antigen-induced expression is greatly increased
|
• serum IgM levels and IgM expression by peripheral B cells are increased
|
• Peyer's patches are larger and more distinct
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• induction of recombination in pre-B cells does not produce an altered phenotype
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• splenomegaly results from
|
• extensive lympho-proliferation of both T and B cells results in splenomegaly
|
• mice have hyperimmunoglobulinemia
|
• splenomegaly results from
|
• extensive lympho-proliferation of both T and B cells results in splenomegaly
|
• mice have hyperimmunoglobulinemia
|
• splenomegaly results from
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• mice exhibit a normal response to LPS injection and T. muris infection
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
Gt(ROSA)26Sortm2(Lmp1/CD40)Uzs/Gt(ROSA)26Sor+ Cd19tm1(cre)Cgn/Cd19+ mice develop mono- and oligoclonal lymphomas
• at 8 weeks
• extreme in mice older than 12 months showing signs of disease
|
• 3.5-fold at 8 weeks
• 20- to 40-fold in mice older than 12 months showing signs of disease
|
• 8 times more in the spleen
• 4-fold in lymph nodes
• increased percent of IgM+IgD+ B cells in the spleen and lymph nodes
• however, absolute numbers in the bone marrow are normal
|
• 3 times more in the spleen
|
• enlarged
|
• prolonged survival in vitro
|
• Ig class switch recombination is achieved in the presence of IL4 indicating constitutive CD40 signaling
|
• activated B cells in the spleen and lymph node
|
• spontaneous
|
• activated T cells with a shift toward activated and memory-type T cells
|
• in mice older than 12 months showing signs of disease
|
• following immunization with hapten conjugated to the carrier chicken gammaglobulin, mice exhibit reduced recruitment/maintenance of B cells within the germinal centers of the spleen compared with wild-type mice
|
• with extreme splenomegaly, enlarged inguinal lymph nodes, hepatomegaly and nodular infiltrates in the kidney, lung and liver in mice older than 12 months showing signs of disease
|
• in mice older than 12 months showing signs of disease
|
• at 8 weeks
• extreme in mice older than 12 months showing signs of disease
|
• 3.5-fold at 8 weeks
• 20- to 40-fold in mice older than 12 months showing signs of disease
|
• 8 times more in the spleen
• 4-fold in lymph nodes
• increased percent of IgM+IgD+ B cells in the spleen and lymph nodes
• however, absolute numbers in the bone marrow are normal
|
• 3 times more in the spleen
|
• enlarged
|
• prolonged survival in vitro
|
• Ig class switch recombination is achieved in the presence of IL4 indicating constitutive CD40 signaling
|
• activated B cells in the spleen and lymph node
|
• spontaneous
|
• activated T cells with a shift toward activated and memory-type T cells
|
• in mice older than 12 months showing signs of disease
|
• at 8 weeks
• extreme in mice older than 12 months showing signs of disease
|
• 3.5-fold at 8 weeks
• 20- to 40-fold in mice older than 12 months showing signs of disease
|
• spontaneous
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• mice show rescue of the defect in peripheral B cells, with an increase in total peripheral B cells, mature B cells, and follicular and MZ B cells
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• 2 weeks after treatment with a cocktail of depleting antibodies (anti-CD4, anti-CD8 and anti-Thy1)
|
• 2 weeks after treatment with a cocktail of depleting antibodies (anti-CD4, anti-CD8 and anti-Thy1)
|
• impaired in the bone marrow
|
• at 6 to 12 weeks in the bone marrow
|
• at 6 to 12 weeks in the spleen and bone marrow
• absent CD19+Fas+ B cells at 8 to 11 weeks in the spleen
|
• at 6 to 12 weeks in the bone marrow
|
• at 6 to 12 weeks in the bone marrow
|
• at P8, mice exhibit an increase in CD19+ B cells in the spleen compared with control mice
|
• at P8, but not P3, in the spleen
• of activated T cells in the bone marrow at 6 to 12 weeks
|
• at P8, but not P3, in the spleen
• of activated T cells in the bone marrow at 6 to 12 weeks
|
• after 2 weeks, mice treated with a cocktail of depleting antibodies (anti-CD4, anti-CD8 and anti-Thy1) exhibit splenomegaly and become terminally ill unlike control mice
|
• after 2 weeks, mice treated with a cocktail of depleting antibodies (anti-CD4, anti-CD8 and anti-Thy1) exhibit rapid expansion of Lmp1+ B cell blasts largely confined to peripheral lymphoid organs and the bone marrow with some infiltration into the liver and rarely into lungs and kidneys compared with control mice
• however, mice treated with one depleting antibodies (anti-CD4, anti-CD8, anti-Thy1 or anti-CD4 and anti-CD8) do not exhibit expansion of B cells
|
• the CD8+ compartment of the bone marrow of mice treated with a cocktail of depleting antibodies (anti-CD4, anti-CD8 and anti-Thy1) exhibit a 2-fold increase in cells expressing IFN-gamma, TNF-alpha, IL4 and IL17
|
• after 2 weeks, mice treated with a cocktail of depleting antibodies (anti-CD4, anti-CD8 and anti-Thy1) exhibit rapid expansion of Lmp1+ B cell blasts largely confined to peripheral lymphoid organs and the bone marrow with some infiltration into the liver and rarely into lungs and kidneys compared with control mice
• however, mice treated with one depleting antibodies (anti-CD4, anti-CD8, anti-Thy1 or anti-CD4 and anti-CD8) do not exhibit expansion of B cells
|
• 2 weeks after treatment with a cocktail of depleting antibodies (anti-CD4, anti-CD8 and anti-Thy1)
|
• impaired in the bone marrow
|
• at 6 to 12 weeks in the bone marrow
|
• at 6 to 12 weeks in the spleen and bone marrow
• absent CD19+Fas+ B cells at 8 to 11 weeks in the spleen
|
• at 6 to 12 weeks in the bone marrow
|
• at 6 to 12 weeks in the bone marrow
|
• at P8, mice exhibit an increase in CD19+ B cells in the spleen compared with control mice
|
• at P8, but not P3, in the spleen
• of activated T cells in the bone marrow at 6 to 12 weeks
|
• at P8, but not P3, in the spleen
• of activated T cells in the bone marrow at 6 to 12 weeks
|
• the CD8+ compartment of the bone marrow of mice treated with a cocktail of depleting antibodies (anti-CD4, anti-CD8 and anti-Thy1) exhibit a 2-fold increase in cells expressing IFN-gamma, TNF-alpha, IL4 and IL17
|
• after 2 weeks, mice treated with a cocktail of depleting antibodies (anti-CD4, anti-CD8 and anti-Thy1) exhibit rapid expansion of Lmp1+ B cell blasts largely confined to peripheral lymphoid organs and the bone marrow with some infiltration into the liver and rarely into lungs and kidneys compared with control mice
• however, mice treated with one depleting antibodies (anti-CD4, anti-CD8, anti-Thy1 or anti-CD4 and anti-CD8) do not exhibit expansion of B cells
|
• 2 weeks after treatment with a cocktail of depleting antibodies (anti-CD4, anti-CD8 and anti-Thy1)
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• in a competitive fitness assay upon activation
|
• 4-fold reduction, not restricted to a particular B cell subtype
• 4-fold reduction of CD3+ splenic B cells
|
• in the bone marrow
|
• in a competitive fitness assay upon activation
|
• in a competitive fitness assay upon activation
|
• 4-fold reduction, not restricted to a particular B cell subtype
• 4-fold reduction of CD3+ splenic B cells
|
• in the bone marrow
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• at 10 months
|
• at 10 months
|
• of age-dependent B cells
|
• in aged mice
|
• broad range of autoantibodies in aged mice
|
• in aged mice
|
• in aged mice with increased cellularity and mesangial matrix and infiltration of Mac1+ cells
|
• in aged mice with increased cellularity and mesangial matrix and infiltration of Mac1+ cells
|
• in aged mice
|
• at 10 months
|
• at 10 months
|
• of age-dependent B cells
|
• in aged mice
|
• at 10 months
|
• at 10 months
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• mutants show high sensitivity to the lethal effects of blood-borne Staphylococcus aureus infection
|
• affected differentiation of T2 B cells, indicated by a reduced population of marginal zone B (MZB) cells and an increased population of follicular B cells
|
• loss of marginal zone B cells
(J:76240)
• decreased numbers of marginal zone B cells
(J:121523)
|
• increased numbers of follicular B cells in spleen
(J:121523)
|
• 3-fold increase in serum IgG3
|
• increased mortality rate after blood-born bacterial infection
|
• mutants show high sensitivity to the lethal effects of blood-borne Staphylococcus aureus infection
|
• affected differentiation of T2 B cells, indicated by a reduced population of marginal zone B (MZB) cells and an increased population of follicular B cells
|
• loss of marginal zone B cells
(J:76240)
• decreased numbers of marginal zone B cells
(J:121523)
|
• increased numbers of follicular B cells in spleen
(J:121523)
|
• 3-fold increase in serum IgG3
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• the number of plasma cells in bone marrow were severely reduced
• the numbers of mature B cells and plasma cells in spleen were normal
|
• the number of plasma cells in bone marrow were severely reduced
• the numbers of mature B cells and plasma cells in spleen were normal
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• B cells expressing B220, CD38 and CD21 are present in lower numbers
• fewer B cells enter S phase after stimulation with anti-IgM, anti-CD40, LPS or CpG DNA
|
• width of marginal zone B cell area is smaller than in controls
|
• mice have a much lower frequency of B220+CD21hiCD23low marginal zone B cells
|
• mice show defective MAP kinase activation in B cells
|
• more mutant B cells undergo apoptosis ex vivo even after stimulation with LPS, CpG DNA or anti-CD40
|
• B cells stimulated with LPS or CpG DNA show a lower proliferative response than controls
|
• all isotypes except IgG2a and IgG2b are significantly lower than in controls
|
• after immunization with TNP-ficoll or TNP-chicken gammaglobulin mice produce less serum TNP-specific IgM and IgG3
|
• B cells expressing B220, CD38 and CD21 are present in lower numbers
• fewer B cells enter S phase after stimulation with anti-IgM, anti-CD40, LPS or CpG DNA
|
• width of marginal zone B cell area is smaller than in controls
|
• mice have a much lower frequency of B220+CD21hiCD23low marginal zone B cells
|
• mice show defective MAP kinase activation in B cells
|
• more mutant B cells undergo apoptosis ex vivo even after stimulation with LPS, CpG DNA or anti-CD40
|
• B cells stimulated with LPS or CpG DNA show a lower proliferative response than controls
|
• all isotypes except IgG2a and IgG2b are significantly lower than in controls
|
• more mutant B cells undergo apoptosis ex vivo even after stimulation with LPS, CpG DNA or anti-CD40
|
• B cells stimulated with LPS or CpG DNA show a lower proliferative response than controls
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• decrease in the number of B220+CD5+ B-1 B cells in the peritoneal cavity
|
• impaired B cell survival following LPS or CpG DNA stimulation or B cell receptor crosslinking
|
• decreased LPS- and/or CpG DNA-induced proliferation in follicular and marginal zone B-2 cells with impaired entry in S phase; however, LPS- and/or CpG DNA-induced IL6 production is similar to wild-type
• decreased proliferation in response to B cell receptor and CD40 stimulation with impaired entry into S phase and impaired survival following B cell receptor crosslinking
|
• decrease for all isotypes except IgM
|
• decreased levels of IgG1 and IgG3 following T cell dependent or T cell independent antigen stimulation, respectively; however, levels of IgM are similar to control following T cell dependent antigen stimulation
|
• decrease in the number of B220+CD5+ B-1 B cells in the peritoneal cavity
|
• impaired B cell survival following LPS or CpG DNA stimulation or B cell receptor crosslinking
|
• decreased LPS- and/or CpG DNA-induced proliferation in follicular and marginal zone B-2 cells with impaired entry in S phase; however, LPS- and/or CpG DNA-induced IL6 production is similar to wild-type
• decreased proliferation in response to B cell receptor and CD40 stimulation with impaired entry into S phase and impaired survival following B cell receptor crosslinking
|
• decrease for all isotypes except IgM
|
• decreased levels of IgG1 and IgG3 following T cell dependent or T cell independent antigen stimulation, respectively; however, levels of IgM are similar to control following T cell dependent antigen stimulation
|
• decreased LPS- and/or CpG DNA-induced proliferation in follicular and marginal zone B-2 cells with impaired entry in S phase; however, LPS- and/or CpG DNA-induced IL6 production is similar to wild-type
• decreased proliferation in response to B cell receptor and CD40 stimulation with impaired entry into S phase and impaired survival following B cell receptor crosslinking
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• normal numbers of mature B cells including follicular and marginal zone B cells are produced
• spleens contain well-organized lymphoid architecture with normal follicles and distinct marginal zone
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• 1-2 days after crosslinking with BCR, there are less apoptotic cells than in purified wild-type B cell cultures
|
• 1-2 days after crosslinking with BCR, there are more cells is S phase than in wild-type B cell cultures
|
• B cell numbers are increased in spleens (130 x 106) compared to wild-type (56 x 106)
|
• B cell hyperplasia is observed, with a significantly expanded population of marginal zone B cells
|
• cells on average have a longer lifespan than wild-type B cells
|
• 1-2 days after crosslinking with BCR, there are less apoptotic cells than in purified wild-type B cell cultures
|
• B cell numbers are increased in spleens (130 x 106) compared to wild-type (56 x 106)
|
• B cell hyperplasia is observed, with a significantly expanded population of marginal zone B cells
|
• cells on average have a longer lifespan than wild-type B cells
|
• 1-2 days after crosslinking with BCR, there are less apoptotic cells than in purified wild-type B cell cultures
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• mice have normal numbers of pre-B cells and mature B cells in the bone marrow
• B cells from the spleen show significant proliferative responses to mitogenic agents
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• naive B cells express 50% - 90% less H-2Kb and have decreased H-2Db expression
• however, B cell development, survival, and proliferative responses are similar to control mice and mice raise normal titers of IgG
|
• naive B cells express 50% - 90% less H-2Kb and have decreased H-2Db expression
• however, B cell development, survival, and proliferative responses are similar to control mice and mice raise normal titers of IgG
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• at 7 to 11 months of age
|
• fewer CD23+CD21+IgM+ follicular B cells are detected
|
• fewer CD211hiIgMhiCD1dhi marginal zone B cells are detected
|
• at 7 to 11 months of age
|
• at 7 to 11 months of age
|
• at 7 to 11 months of age
|
• at 7 to 11 months of age
|
• at 7 to 11 months of age
|
• at 7 to 11 months of age
|
• following stimulation by anti-IgM or anti-CD40 antibodies, B cell proliferation is reduced
• however, proliferation stimulated by LPS is normal
|
• antibody-mediated response to NP-CG is not as strong ad in wild-type mice
• antibody-mediated response to NP-ficoll is severely impaired
|
• at 7 to 11 months of age, mice develop an autoimmune disease with features similar to systemic lupus erythematosus
|
• following stimulation by anti-IgM or anti-CD40 antibodies, B cell proliferation is reduced
• however, proliferation stimulated by LPS is normal
|
• at 7 to 11 months of age
|
• at 7 to 11 months of age
|
• fewer CD23+CD21+IgM+ follicular B cells are detected
|
• fewer CD211hiIgMhiCD1dhi marginal zone B cells are detected
|
• at 7 to 11 months of age
|
• at 7 to 11 months of age
|
• at 7 to 11 months of age
|
• at 7 to 11 months of age
|
• at 7 to 11 months of age
|
• following stimulation by anti-IgM or anti-CD40 antibodies, B cell proliferation is reduced
• however, proliferation stimulated by LPS is normal
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• following immunization, fewer peanut agglutinin positive (PNA+) clusters are present and very few IgD- areas typical of germinal centers are identified
• B cell follicle disruption is not as severe as in Ltb null mice
• however, some follicular dendritic cells are present and immune complex binding is observed
|
• follicular dendritic cell (FDC) networks are reduced to 15% to 20% of the number found in wild-type mice
|
• following exposure to sheep red blood cells (SRBC) mice fail to develop normal specific IgG responses
• memory IgG responses are reduced compared to wild-type but not as much as in Ltb null mice
• affinity maturation is only slightly reduced
• however, unlike Ltb null mice IgM levels are normal
|
• following immunization, fewer peanut agglutinin positive (PNA+) clusters are present and very few IgD- areas typical of germinal centers are identified
• B cell follicle disruption is not as severe as in Ltb null mice
• however, some follicular dendritic cells are present and immune complex binding is observed
|
• follicular dendritic cell (FDC) networks are reduced to 15% to 20% of the number found in wild-type mice
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• mice lack follicular dendritic cells and no immune complex binding is observed
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
|
• unlike other conditional knockouts of Apcs, mice exhibit normal numbers of NK T cells, normal antibody response and normal germinal center B cell numbers
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• there is almost a 2-fold increase in the number of follicular B cells found in the spleen
|
• there are greatly increased numbers of marginal zone B cells in both spleen and lymph nodes
• surface expression of CD21 on these cells is enhanced
|
• 50% of B cells remain viable in unsupplemented culture for up to 10 days compared to no survival of wild-type cells
|
• about a 3-fold increase in the number of cells present in lymph nodes
• increase is due to expansion of the B cell compartment
|
• there is almost a 2-fold increase in the number of follicular B cells found in the spleen
|
• there are greatly increased numbers of marginal zone B cells in both spleen and lymph nodes
• surface expression of CD21 on these cells is enhanced
|
• 50% of B cells remain viable in unsupplemented culture for up to 10 days compared to no survival of wild-type cells
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• the number of mature peripheral B cells is increased resulting enlargement of the spleen and lymph nodes
• however, B cell proliferation is normal
|
• the number of mature peripheral B cells is increased resulting enlargement of the spleen and lymph nodes
• however, B cell proliferation is normal
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• in the peritoneal cavity
|
• the spleen contains 6-fold more AA4.1-B cells than in control mice due to enhanced survival
• however, B cell proliferation is normal
|
• lymphoid cells appear to spill over their normal confines into surrounding tissue unlike in wild-type mice
|
• in the peritoneal cavity
|
• the spleen contains 6-fold more AA4.1-B cells than in control mice due to enhanced survival
• however, B cell proliferation is normal
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• B cells, but not dendritic cells or macrophages, are capable of inducing proliferation of CD4+ T cells containing Tg(Tcra2D2,Tcrb2D2)1Kuch in vitro unlike wild-type cells
• unlike in vitro, when CD4+ T cells containing Tg(Tcra2D2,Tcrb2D2)1Kuch are transferred into mice they fail to exhibit proliferation and instead undergo cell death
• mice are capable of inducing proliferation of memory T cells expressing Tg(Tcra2D2,Tcrb2D2)1Kuch unlike wild type mice
• mice are capable of inducing proliferation of Tg(Tcra2D2,Tcrb2D2)1Kuch T cells also deficient in Pdcd1 (Pdcd1tm1Hon) up to 71% or following treatment with anti-CTLA-4 antibodies up to 79% and proliferation is increased to 97% when both are used
• B cells induce peripheral tolerance by sensitizing T cells to antigen induced cell death in adoptive transfer experiments
|
• mice are resistant to direct and passive MOG-induced experimental autoimmune encephalomyelitis (EAE) and can confer some resistance upon adoptive transfer of B cells into wild-type micemice are resistant to direct and passive MOG-induced experimental encephalomyelitis (EAE) and can confer some resistance upon adoptive transfer of B cells into wild-type mice
• resistance to EAE is not affected by depletion of T regulatory cells
• however, mice inoculated with C57BL/6 spinal cord fluid develop EAE
|
• B cells, but not dendritic cells or macrophages, are capable of inducing proliferation of CD4+ T cells containing Tg(Tcra2D2,Tcrb2D2)1Kuch in vitro unlike wild-type cells
• unlike in vitro, when CD4+ T cells containing Tg(Tcra2D2,Tcrb2D2)1Kuch are transferred into mice they fail to exhibit proliferation and instead undergo cell death
• mice are capable of inducing proliferation of memory T cells expressing Tg(Tcra2D2,Tcrb2D2)1Kuch unlike wild type mice
• mice are capable of inducing proliferation of Tg(Tcra2D2,Tcrb2D2)1Kuch T cells also deficient in Pdcd1 (Pdcd1tm1Hon) up to 71% or following treatment with anti-CTLA-4 antibodies up to 79% and proliferation is increased to 97% when both are used
• B cells induce peripheral tolerance by sensitizing T cells to antigen induced cell death in adoptive transfer experiments
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• unlike in vitro, when CD4+ T cells containing Tg(Tcra2D2,Tcrb2D2)1Kuch are transferred into mice they fail to exhibit proliferation
|
• mice are resistant to direct and passive MOG-induced experimental autoimmune encephalomyelitis
|
• unlike in vitro, when CD4+ T cells containing Tg(Tcra2D2,Tcrb2D2)1Kuch are transferred into mice they fail to exhibit proliferation
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• B cell turnover over a one week period is almost twice that of controls
|
• immature B cell numbers in the spleen are reduced by about a half
|
• there is a 2- to 4- fold reduction in the number of mature recirculating B cells found in the bone marrow
• the IgMlowIgD+ mature B cell population is strongly diminished in the spleen by 3- to 4- fold
• B cell numbers in the lymph nodes are also strongly reduced
|
• B-1 B cell numbers are strongly decreased in the peritoneum cavity
|
• follicular B cells are the most diminished B cell population in the spleen
|
• marginal zone B cell numbers are reduced about 4-fold
|
• B cell turnover over a one week period is almost twice that of controls
|
• immature B cell numbers in the spleen are reduced by about a half
|
• there is a 2- to 4- fold reduction in the number of mature recirculating B cells found in the bone marrow
• the IgMlowIgD+ mature B cell population is strongly diminished in the spleen by 3- to 4- fold
• B cell numbers in the lymph nodes are also strongly reduced
|
• B-1 B cell numbers are strongly decreased in the peritoneum cavity
|
• follicular B cells are the most diminished B cell population in the spleen
|
• marginal zone B cell numbers are reduced about 4-fold
|
• B cell turnover over a one week period is almost twice that of controls
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• there is a 2- to 4- fold reduction in the number of mature recirculating B cells found in the bone marrow
• the IgMlowIgD+ mature B cell population is strongly diminished in the spleen by 3- to 4- fold
• B cell numbers in the lymph nodes are also strongly reduced
|
• B-1 B cell numbers are strongly decreased in the peritoneum cavity
|
• follicular B cells are the most diminished B cell population in the spleen
|
• marginal zone B cell numbers are reduced about 4-fold
|
• there is a 2- to 4- fold reduction in the number of mature recirculating B cells found in the bone marrow
• the IgMlowIgD+ mature B cell population is strongly diminished in the spleen by 3- to 4- fold
• B cell numbers in the lymph nodes are also strongly reduced
|
• B-1 B cell numbers are strongly decreased in the peritoneum cavity
|
• follicular B cells are the most diminished B cell population in the spleen
|
• marginal zone B cell numbers are reduced about 4-fold
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
|
• B cell turnover over a one week period is twice that of controls
|
|
• immature B cell numbers in the spleen are reduced by about a third
|
|
• there is a 2- to 4- fold reduction in the number of mature recirculating B cells found in the bone marrow
• the IgMlowIgD+ mature B cell population is strongly diminished in the spleen by 3- to 4- fold
• B cell numbers in the lymph nodes are also strongly reduced
|
|
• B-1 B cell numbers are strongly decreased in the peritoneum cavity
|
|
• follicular B cells are the most diminished B cell population in the spleen
|
|
• marginal zone B cell numbers are reduced about 4-fold
|
|
• B cell turnover over a one week period is twice that of controls
|
|
• immature B cell numbers in the spleen are reduced by about a third
|
|
• there is a 2- to 4- fold reduction in the number of mature recirculating B cells found in the bone marrow
• the IgMlowIgD+ mature B cell population is strongly diminished in the spleen by 3- to 4- fold
• B cell numbers in the lymph nodes are also strongly reduced
|
|
• B-1 B cell numbers are strongly decreased in the peritoneum cavity
|
|
• follicular B cells are the most diminished B cell population in the spleen
|
|
• marginal zone B cell numbers are reduced about 4-fold
|
|
• B cell turnover over a one week period is twice that of controls
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• B cells are resistant to Fas-mediated programmed cell death compared to controls
|
• moderate expansion of T cells
|
• increase in the number and size of anti-DNA producing B cells
|
• small decrease in the percentage of IgM+B cells in the bone marrow, reflecting a reduction in mature or recirculating B cells
|
• moderate increase in B cells
|
• increase in percentage of splenic plasma cells
|
• percentage of B-1a cells in the peritoneal cavity is lower than in controls but the absolute numbers are not different
|
• spontaneous B cell activation becomes apparent at 6 months of age
|
• B cells are hyperresponsive to multiple stimuli
• B cells exhibit exaggerated NF-kappaB responses to CD40-induced signals
|
• increase in glomerular immunoglobulin deposits
|
• modest increase in IgGs
|
• increase in IL-6 production by B cells after treatment with LPS and CpG
|
• CpG treatment enhances production of IgG dsDNA antibodies in serum as well as deposition of IgG in renal glomeruli, indicating development of autoimmune disease
• IgM deposits are seen in the kidneys
|
• mice develop autoimmunity; antibodies to over 46 self-antigens are detected, including antibodies to nuclear antigens
|
• B cells are resistant to Fas-mediated programmed cell death compared to controls
|
• moderate expansion of T cells
|
• increase in the number and size of anti-DNA producing B cells
|
• small decrease in the percentage of IgM+B cells in the bone marrow, reflecting a reduction in mature or recirculating B cells
|
• moderate increase in B cells
|
• increase in percentage of splenic plasma cells
|
• percentage of B-1a cells in the peritoneal cavity is lower than in controls but the absolute numbers are not different
|
• spontaneous B cell activation becomes apparent at 6 months of age
|
• B cells are hyperresponsive to multiple stimuli
• B cells exhibit exaggerated NF-kappaB responses to CD40-induced signals
|
• increase in glomerular immunoglobulin deposits
|
• modest increase in IgGs
|
• B cells are resistant to Fas-mediated programmed cell death compared to controls
|
• B cells are hyperresponsive to multiple stimuli
• B cells exhibit exaggerated NF-kappaB responses to CD40-induced signals
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• B cells are resistant to Fas-mediated programmed cell death compared to controls
|
• increase in percentage of splenic plasma cells
|
• IgM and IgG deposits are seen in the kidneys
|
• CpG treatment enhances production of IgG dsDNA antibodies in serum as well as deposition of IgG in renal glomeruli, indicating development of autoimmune disease
|
• B cells are resistant to Fas-mediated programmed cell death compared to controls
|
• increase in percentage of splenic plasma cells
|
• IgM and IgG deposits are seen in the kidneys
|
• B cells are resistant to Fas-mediated programmed cell death compared to controls
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• mice exhibit normal germinal center B cell numbers, NP-specific IgG1 titers, and immune memory response after immunization
|
• after NP-CGG immunization, antigen-specific IgE titers are increased 30-fold compared to in similarly treated wild-type mice
|
• after NP-CGG immunization, antigen-specific IgE titers are increased 30-fold compared to in similarly treated wild-type mice
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• spleen and lymph node sizes are normal
• mice exhibit normal T-dependent and T-independent antibody responses
|
• the proportion of AA4-B220+IgMlow CD19+ follicular B cells is decreased compared to in control mice
|
• the frequency of CD19+B220+ B cells is increased compared to in control mice
• the number of total peritoneal B cells is increased compared to in control mice
|
• the frequency of B220+AA4+ transitional B cells is increased compared to in control mice
• the absolute number of transitional B cells is increased compared to in control mice
|
• in the peritoneum
|
• the absolute number of follicular B cells is increased compared to in control mice
|
• mice exhibit enlarged marginal zones surrounding white pulp follicles compared with control mice
|
• the frequency of AA4-B220+IgMhi CD19+ marginal zone B cells is increased compared to in control mice
• the absolute number of marginal zone B cells is increased compared to in control mice
|
• the proportion of AA4-B220+IgMlow CD19+ follicular B cells is decreased compared to in control mice
|
• the frequency of CD19+B220+ B cells is increased compared to in control mice
• the number of total peritoneal B cells is increased compared to in control mice
|
• the frequency of B220+AA4+ transitional B cells is increased compared to in control mice
• the absolute number of transitional B cells is increased compared to in control mice
|
• in the peritoneum
|
• the absolute number of follicular B cells is increased compared to in control mice
|
• mice exhibit enlarged marginal zones surrounding white pulp follicles compared with control mice
|
• the frequency of AA4-B220+IgMhi CD19+ marginal zone B cells is increased compared to in control mice
• the absolute number of marginal zone B cells is increased compared to in control mice
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• 2 weeks after treatment with a cocktail of depleting antibodies (anti-CD4, anti-CD8 and anti-Thy1)
|
• 2 weeks after treatment with a cocktail of depleting antibodies (anti-CD4, anti-CD8 and anti-Thy1)
|
• impaired in the bone marrow
|
• at 6 to 12 weeks in the bone marrow
|
• at 6 to 12 weeks in the spleen and bone marrow
• absent CD19+Fas+ B cells at 8 to 11 weeks in the spleen
|
• at 6 to 12 weeks in the bone marrow
|
• at 6 to 12 weeks in the bone marrow
|
• at P8, mice exhibit an increase in CD19+ B cells in the spleen compared with control mice
|
• at P8, but not P3, in the spleen
• of activated T cells in the bone marrow at 6 to 12 weeks
|
• at P8, but not P3, in the spleen
• of activated T cells in the bone marrow at 6 to 12 weeks
|
• after 2 weeks, mice treated with a cocktail of depleting antibodies (anti-CD4, anti-CD8 and anti-Thy1) exhibit splenomegaly and become terminally ill unlike control mice
|
• after 2 weeks, mice treated with a cocktail of depleting antibodies (anti-CD4, anti-CD8 and anti-Thy1) exhibit rapid expansion of Lmp1+ B cell blasts largely confined to peripheral lymphoid organs and the bone marrow with some infiltration into the liver and rarely into lungs and kidneys compared with control mice
• however, mice treated with one depleting antibodies (anti-CD4, anti-CD8, anti-Thy1 or anti-CD4 and anti-CD8) do not exhibit expansion of B cells
|
• in an in vitro tumor killing assay, CD4+ T cells exhibit reduced tumor killing compared with control cells
• however, CD4+ T cells exhibit normal prevention of tumor outgrowth in vivo and elimination of nontransformed L,p1+ B cells upon transfer
|
• the CD8+ compartment of the bone marrow of mice treated with a cocktail of depleting antibodies (anti-CD4, anti-CD8 and anti-Thy1) exhibit a 2-fold increase in cells expressing IFN-gamma, TNF-alpha, IL4 and IL17
• in vivo, CD8+ T cells exhibit reduced prevention of tumor outgrowth compared with control cells
• however, CD8+ T cell exhibit normal tumor killing in vitro and elimination of nontransformed L,p1+ B cells upon transfer
|
• minor in T cells co-cultured with tumor or B cells
|
• minor in T cells co-cultured with tumor or B cells
|
• after 2 weeks, mice treated with a cocktail of depleting antibodies (anti-CD4, anti-CD8 and anti-Thy1) exhibit rapid expansion of Lmp1+ B cell blasts largely confined to peripheral lymphoid organs and the bone marrow with some infiltration into the liver and rarely into lungs and kidneys compared with control mice
• however, mice treated with one depleting antibodies (anti-CD4, anti-CD8, anti-Thy1 or anti-CD4 and anti-CD8) do not exhibit expansion of B cells
|
• 2 weeks after treatment with a cocktail of depleting antibodies (anti-CD4, anti-CD8 and anti-Thy1)
|
• impaired in the bone marrow
|
• at 6 to 12 weeks in the bone marrow
|
• at 6 to 12 weeks in the spleen and bone marrow
• absent CD19+Fas+ B cells at 8 to 11 weeks in the spleen
|
• at 6 to 12 weeks in the bone marrow
|
• at 6 to 12 weeks in the bone marrow
|
• at P8, mice exhibit an increase in CD19+ B cells in the spleen compared with control mice
|
• at P8, but not P3, in the spleen
• of activated T cells in the bone marrow at 6 to 12 weeks
|
• at P8, but not P3, in the spleen
• of activated T cells in the bone marrow at 6 to 12 weeks
|
• in an in vitro tumor killing assay, CD4+ T cells exhibit reduced tumor killing compared with control cells
• however, CD4+ T cells exhibit normal prevention of tumor outgrowth in vivo and elimination of nontransformed L,p1+ B cells upon transfer
|
• the CD8+ compartment of the bone marrow of mice treated with a cocktail of depleting antibodies (anti-CD4, anti-CD8 and anti-Thy1) exhibit a 2-fold increase in cells expressing IFN-gamma, TNF-alpha, IL4 and IL17
• in vivo, CD8+ T cells exhibit reduced prevention of tumor outgrowth compared with control cells
• however, CD8+ T cell exhibit normal tumor killing in vitro and elimination of nontransformed L,p1+ B cells upon transfer
|
• 2 weeks after treatment with a cocktail of depleting antibodies (anti-CD4, anti-CD8 and anti-Thy1)
|
• after 2 weeks, mice treated with a cocktail of depleting antibodies (anti-CD4, anti-CD8 and anti-Thy1) exhibit rapid expansion of Lmp1+ B cell blasts largely confined to peripheral lymphoid organs and the bone marrow with some infiltration into the liver and rarely into lungs and kidneys compared with control mice
• however, mice treated with one depleting antibodies (anti-CD4, anti-CD8, anti-Thy1 or anti-CD4 and anti-CD8) do not exhibit expansion of B cells
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• mice exhibit normal class switch recombination
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• peritoneal B-1a cell numbers are further reduced over reduction seen in Tab2 KO mice
|
• plasma cell populations are reduced
|
• undergo apoptosis more rapidly in response to CpG DNA and anti-IgM but not anti-CD40 stimulation
|
• impaired proliferation in response to CpG DNA, anti-IgM, and anti-CD40 stimulation
|
• impaired production
|
• undergo apoptosis more rapidly in response to CpG DNA and anti-IgM but not anti-CD40 stimulation
|
• impaired proliferation in response to CpG DNA, anti-IgM, and anti-CD40 stimulation
|
• peritoneal B-1a cell numbers are further reduced over reduction seen in Tab2 KO mice
|
• plasma cell populations are reduced
|
• undergo apoptosis more rapidly in response to CpG DNA and anti-IgM but not anti-CD40 stimulation
|
• impaired proliferation in response to CpG DNA, anti-IgM, and anti-CD40 stimulation
|
• impaired production
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
|
• unimmunized mice exhibit normal numbers of bone marrow B cell subpopulations, splenic follicular B cells and marginal zone B cells
• mice immunized with sheep red blood cell exhibit normal numbers of transitional and marginal zone B cells
|
|
• modest impairment in affinity maturation
• however, somatic hypermutation is normal
|
|
• 3-fold in the spleen and also in the mesenteric lymph nodes of mice immunized with sheep red blood cell
• in mice challenged with NP-KLH
|
|
• in the spleen and lymph nodes of mice immunized with sheep red blood cell
|
|
• in the bone marrow of mice immunized with sheep red blood cell
|
|
• in mice immunized with sheep red blood cell
• in mice challenged with NP-KLH
|
|
• in mice immunized with sheep red blood cell
• in mice challenged with NP-KLH
|
|
• 10-fold less in mice challenged with NP-KLH
|
|
• 10-fold less in mice challenged with NP-KLH
|
|
• modest impairment in affinity maturation
• however, somatic hypermutation is normal
|
|
• 3-fold in the spleen and also in the mesenteric lymph nodes of mice immunized with sheep red blood cell
• in mice challenged with NP-KLH
|
|
• in the spleen and lymph nodes of mice immunized with sheep red blood cell
|
|
• in the bone marrow of mice immunized with sheep red blood cell
|
|
• in mice immunized with sheep red blood cell
• in mice challenged with NP-KLH
|
|
• in mice immunized with sheep red blood cell
• in mice challenged with NP-KLH
|
|
• 10-fold less in mice challenged with NP-KLH
|
|
• 10-fold less in mice challenged with NP-KLH
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
|
• intermediate at 3 and 6 months in mice immunized with sheep red blood cell
|
|
• intermediate at 3 and 6 months in mice immunized with sheep red blood cell
|
|
• intermediate at 3 and 6 months in mice immunized with sheep red blood cell
|
|
• intermediate at 3 and 6 months in mice immunized with sheep red blood cell
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• mice develop acute leukemia with an incidence of 7% at 12 months of age
• leukemia cells are present in the bone marrow, spleen, lymph nodes and infiltrate multiple organs, including the CNS
• 94% of leukemias have a B cell precursor phenotype
|
• in leukemic mice
|
• progenitor B cells proliferate extensively in methylcellulose culture supplemented with IL-7, SCF, and FLT3 and are severely compromised in the their ability to differentiate into CD43- cells compared with progenitor B cells from controls indicating enhanced proliferation of progenitor B cells
|
• mice show perturbed early B cell progenitor cell differentiation
|
• leukemic blasts are arrested at the pro/pre-B stage of B cell precursor differentiation
|
• in leukemic mice
|
• a lower percentage of B cells are seen in the peripheral blood over a 30 week period in healthy preleukemic mice
|
• decrease in immature and recirculating B cells in the bone marrow in healthy preleukemic mice
|
• leukemic mice present with leukocytosis
|
• enhanced proliferation of progenitor B cells
• preleukemic mice irradiated sublethally to deplete the endogenous B cell populations show regeneration of B cell progenitors with a dramatic expansion of B220lo progenitor cell population indicating enhanced B cell progenitor self-renewal
|
• in leukemic mice
|
• progenitor B cells proliferate extensively in methylcellulose culture supplemented with IL-7, SCF, and FLT3 and are severely compromised in the their ability to differentiate into CD43- cells compared with progenitor B cells from controls indicating enhanced proliferation of progenitor B cells
|
• mice show perturbed early B cell progenitor cell differentiation
|
• leukemic blasts are arrested at the pro/pre-B stage of B cell precursor differentiation
|
• a lower percentage of B cells are seen in the peripheral blood over a 30 week period in healthy preleukemic mice
|
• decrease in immature and recirculating B cells in the bone marrow in healthy preleukemic mice
|
• leukemic mice present with leukocytosis
|
• enhanced proliferation of progenitor B cells
• preleukemic mice irradiated sublethally to deplete the endogenous B cell populations show regeneration of B cell progenitors with a dramatic expansion of B220lo progenitor cell population indicating enhanced B cell progenitor self-renewal
|
• in leukemic mice
|
• in leukemic mice
|
• in leukemic mice
|
• in leukemic mice
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
acute lymphoblastic leukemia | DOID:9952 |
OMIM:247640 OMIM:613065 |
J:226241 |
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• mice exhibit increased penetrance and accelerated acute leukemia development compared to single Tcf3tm1(PBX1)Mlc conditional mutants
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• preleukemic mice show a greater decrease of immature B cells of the Lin-CD19+CD43- fractions compared to Tcf3tm1(PBX1)Mlc conditional mutants, indicating a more severe block of B cell differentiation at this stage of maturation
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• preleukemic mice show expansion of GFP+ progenitor cells of the Lin-CD19+CD43+ fractions at younger ages compared to single Tcf3tm1(PBX1)Mlc conditional mutants, indicating accelerated preleukemic progenitor B cell expansion
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• preleukemic mice show a greater decrease of immature B cells of the Lin-CD19+CD43- fractions compared to Tcf3tm1(PBX1)Mlc conditional mutants, indicating a more severe block of B cell differentiation at this stage of maturation
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• preleukemic mice show a greater decrease of immature B cells of the Lin-CD19+CD43- fractions compared to Tcf3tm1(PBX1)Mlc conditional mutants, indicating a more severe block of B cell differentiation at this stage of maturation
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• preleukemic mice show expansion of GFP+ progenitor cells of the Lin-CD19+CD43+ fractions at younger ages compared to single Tcf3tm1(PBX1)Mlc conditional mutants, indicating accelerated preleukemic progenitor B cell expansion
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• preleukemic mice show a greater decrease of immature B cells of the Lin-CD19+CD43- fractions compared to Tcf3tm1(PBX1)Mlc conditional mutants, indicating a more severe block of B cell differentiation at this stage of maturation
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• a reduction between 30 and 50% in IgA-secreting cells in spleen and bone marrow
• a reduction between 30 and 50% in IgG-secreting cells in the bone marrow
• marker analysis shows a 50% reduction of splenic CD138/Taci+ plasmablast/plasma cell numbers; this decrease is attributed to the approximate 60% decrease in the late CD19-negative mature plasma cell subset
• the number of late CD19-negative P3-plasma cells is reduced in the bone marrow by approximately 50%, but only in the Taci+ plasma cell subset with a high abundance of surface CD138
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• 42 days after NP-KLH immunization, mice show a trend of increased numbers of NP-specific memory B cells (CD38-sIgG+) cells in the spleen and bone marrow
• numbers of pro-B cells, pre-B cells, immature B cells, and recirculating mature B cells in the bone marrow are unaltered in non-immunized mice
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• differentiation of germinal center B cells into plasmablasts is impaired resulting in a decrease in numbers of newly formed plasmablasts after immunization with NP-KLH
• however, the number of germinal center B cells is not altered
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• serum IgA levels are reduced by roughly 50% in non-immunized mice
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• serum IgG levels are reduced by roughly 50% in non-immunized mice
• mice immunized with the thymus-dependent model antigen TNP-KLH show reduced TNP-specific IgG titers
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• serum IgM levels are reduced by roughly 50% in non-immunized mice
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• mice show reduced antigen-specific antibody responses
• TNP-KLH-immunized mice show a 50% reduction in the number of TNP-specific IgG- or IgM-secreting cells in the spleen and bone marrow 70 days after primary immunization
• TNP-KLH-immunized mice show a reduction in the CD138/Taci+ plasmablast/plasma cell population in the spleen and bone marrow, indicating fewer mature P3-plasma cells
• however, the number of P1-plasmablasts and P2-plasma cells in the spleen and bone marrow are not reduced in TNP-KLH-immunized mice
• mice show lower numbers of P1-plasmablasts in the blood 14 days after primary immunization with TNP-KLH
• TNP-KLH immunized mice show a more pronounced shift to CD19+ cells in CD138/Taci+ populations under homeostatic conditions
• the number of CD138low early P2-plasma cells in the bone marrow is elevated in TNP-KLH immunized mice
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• a reduction between 30 and 50% in IgA-secreting cells in spleen and bone marrow
• a reduction between 30 and 50% in IgG-secreting cells in the bone marrow
• marker analysis shows a 50% reduction of splenic CD138/Taci+ plasmablast/plasma cell numbers; this decrease is attributed to the approximate 60% decrease in the late CD19-negative mature plasma cell subset
• the number of late CD19-negative P3-plasma cells is reduced in the bone marrow by approximately 50%, but only in the Taci+ plasma cell subset with a high abundance of surface CD138
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• 42 days after NP-KLH immunization, mice show a trend of increased numbers of NP-specific memory B cells (CD38-sIgG+) cells in the spleen and bone marrow
• numbers of pro-B cells, pre-B cells, immature B cells, and recirculating mature B cells in the bone marrow are unaltered in non-immunized mice
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• differentiation of germinal center B cells into plasmablasts is impaired resulting in a decrease in numbers of newly formed plasmablasts after immunization with NP-KLH
• however, the number of germinal center B cells is not altered
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• serum IgA levels are reduced by roughly 50% in non-immunized mice
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• serum IgG levels are reduced by roughly 50% in non-immunized mice
• mice immunized with the thymus-dependent model antigen TNP-KLH show reduced TNP-specific IgG titers
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• serum IgM levels are reduced by roughly 50% in non-immunized mice
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• severely abrogated development of precursors to MZBs in the spleen
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• decreased level of T2 B cells in the spleen
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• modestly increased percentage of T1 cells in the spleen compared with heterozygotes
• normal percentage of total B cells
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• absent marginal zone B cell (MZB) lineage in the spleen
• complete absence of MZBs surrounding the marginal sinus, labeled with the metallophilic macrophage marker 1 in the spleen
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• increased level of follicular B cells in the spleen
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• severely abrogated development of precursors to MZBs in the spleen
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• decreased level of T2 B cells in the spleen
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• modestly increased percentage of T1 cells in the spleen compared with heterozygotes
• normal percentage of total B cells
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• absent marginal zone B cell (MZB) lineage in the spleen
• complete absence of MZBs surrounding the marginal sinus, labeled with the metallophilic macrophage marker 1 in the spleen
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• increased level of follicular B cells in the spleen
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• GFP+ pre-B cells are absent in the bone marrow
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• GFP+ pre-B cells are absent in the bone marrow
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• decrease in the frequency and absolute number of immature B cells
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• decrease in the frequency of B1 cells in the peritoneal cavity
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• increase in B-cell frequencies in spleen, inguinal lymph nodes, and peritoneal cavity
• increase in absolute numbers of B cells
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• increase in the frequency and absolute number of mature B cells
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• increase in the frequency of B2 cells in the peritoneal cavity
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• within the mature B-cell population, marginal zone (MZ) B cells are increased
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• decrease in T-cell frequencies in spleen, inguinal lymph nodes, and peritoneal cavity
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• while the reduced frequency of follicular B cells is due to the expansion of MZ cell population, the absolute number of follicular B cells is not reduced, but is even increased
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• B cells exhibit increased expression of surface molecules (MHCII, CD86, CD23, CD21, and ICOSL) associated with B-cell activation
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• antibody deposition to kidney glomeruli is seen in 10 month old mice, but not in 8 week old mice
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• increase in serum and fecal IgA concentration
• increase in frequencies of IgA+ B cells in both the spleen and Peyers patches
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• increase in serum IgG2a concentration
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• increase in serum IgG2b concentration
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• increase in serum IgM concentration
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• increase in serum IL-6 concentration at 10 months of age
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• mutant recipient mice transferred with BM12 CD4 T cells show a stronger autoimmune response than wild-type mice, have a higher frequency of germinal center B cells and plasma cells, a higher titer of serum autoantibodies against dsDNA and nuclear antigen, and higher levels of kidney glomerular deposition with IgG
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• mice develop a lupus-like autoimmune disease
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• mice exhibit higher concentration of serum autoantibodies against nuclear antigen at 10 months of age
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• mice exhibit higher concentration of serum autoantibodies against double-stranded DNA (dsDNA) at 10 months of age
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• decrease in the frequency and absolute number of immature B cells
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• decrease in the frequency of B1 cells in the peritoneal cavity
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• increase in B-cell frequencies in spleen, inguinal lymph nodes, and peritoneal cavity
• increase in absolute numbers of B cells
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• increase in the frequency and absolute number of mature B cells
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• increase in the frequency of B2 cells in the peritoneal cavity
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• within the mature B-cell population, marginal zone (MZ) B cells are increased
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• decrease in T-cell frequencies in spleen, inguinal lymph nodes, and peritoneal cavity
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• while the reduced frequency of follicular B cells is due to the expansion of MZ cell population, the absolute number of follicular B cells is not reduced, but is even increased
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• B cells exhibit increased expression of surface molecules (MHCII, CD86, CD23, CD21, and ICOSL) associated with B-cell activation
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• antibody deposition to kidney glomeruli is seen in 10 month old mice, but not in 8 week old mice
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• increase in serum and fecal IgA concentration
• increase in frequencies of IgA+ B cells in both the spleen and Peyers patches
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• increase in serum IgG2a concentration
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• increase in serum IgG2b concentration
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• increase in serum IgM concentration
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• increase in serum IL-6 concentration at 10 months of age
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• germinal center B cells sorted from Peyer's patches of aged mice show a significantly lower mutation frequency at both JH4 and JK5 intronic regions, with a higher proportion of sequences harboring zero or less than 5 mutations and a concomitant decrease in the number of highly mutated clones relative to control mice
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• mice show a marked reduction in the number of splenic resting mature B cells
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• unimmunized mice show a reduced percentage of germinal center B cells (and IgA+ germinal center cells) in Peyer's patches
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• activated B cells exhibit sustained expression of the integrated stress response (ISR) effector activating transcription factor 4 (Atf4) and induction of the ISR transcriptional program, increased cell death, and reduced AID (activation-induced cytidine deaminase) expression relative to control cells
• resting B cells show phosphorylation of Perk and its downstream target eIF2alpha as well as Atf4 expression, indicating constitutive activation of the Perk-mediated ISR pathway
• however, plasma cell differentiation and function are normal under steady-state conditions
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• CaspGLOW staining of cultured splenocytes revealed increased caspase activity at 24 and 48 h after activation with LPS + IL-4 or LPS-BAFF-TGFbeta
• number of live cells in splenocyte cultures is significantly decreased at 48 and 72 h after activation with LPS + IL-4
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• primary splenic B cells show lower levels of class switch recombination (CSR) for all tested isotypes under in vitro conditions that induce switching to IgG1, IgG3, IgG2b or IgA
• CSR defect is due to impaired formation of AID-induced DNA double-strand breaks (DSBs), caused by defective induction of AID expression with further contribution of impaired germline transcription (GLT) in an isotype-specific manner
• percentage of switched IgA germinal center B cells is significantly reduced in Peyer's patches
• however, B cell proliferation is normal under all stimulation conditions, and class switching is reduced independently of the number of cell divisions
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• CaspGLOW staining of cultured splenocytes revealed increased caspase activity at 24 and 48 h after activation with LPS + IL-4 or LPS-BAFF-TGFbeta
• number of live cells in splenocyte cultures is significantly decreased at 48 and 72 h after activation with LPS + IL-4
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• splenocyte cultures show an increased proportion of cells with low mitochondrial membrane potential at 24 and 48 h after activation with LPS + IL-4
• however, no changes are observed in mitochondrial mass or respiration capacity
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• germinal center B cells sorted from Peyer's patches of aged mice show a significantly lower mutation frequency at both JH4 and JK5 intronic regions, with a higher proportion of sequences harboring zero or less than 5 mutations and a concomitant decrease in the number of highly mutated clones relative to control mice
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• mice show a marked reduction in the number of splenic resting mature B cells
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• unimmunized mice show a reduced percentage of germinal center B cells (and IgA+ germinal center cells) in Peyer's patches
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• activated B cells exhibit sustained expression of the integrated stress response (ISR) effector activating transcription factor 4 (Atf4) and induction of the ISR transcriptional program, increased cell death, and reduced AID (activation-induced cytidine deaminase) expression relative to control cells
• resting B cells show phosphorylation of Perk and its downstream target eIF2alpha as well as Atf4 expression, indicating constitutive activation of the Perk-mediated ISR pathway
• however, plasma cell differentiation and function are normal under steady-state conditions
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• CaspGLOW staining of cultured splenocytes revealed increased caspase activity at 24 and 48 h after activation with LPS + IL-4 or LPS-BAFF-TGFbeta
• number of live cells in splenocyte cultures is significantly decreased at 48 and 72 h after activation with LPS + IL-4
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• primary splenic B cells show lower levels of class switch recombination (CSR) for all tested isotypes under in vitro conditions that induce switching to IgG1, IgG3, IgG2b or IgA
• CSR defect is due to impaired formation of AID-induced DNA double-strand breaks (DSBs), caused by defective induction of AID expression with further contribution of impaired germline transcription (GLT) in an isotype-specific manner
• percentage of switched IgA germinal center B cells is significantly reduced in Peyer's patches
• however, B cell proliferation is normal under all stimulation conditions, and class switching is reduced independently of the number of cell divisions
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• mice show a rescue of the B-cell defect seen in Otub1 conditional mice, with mice showing enhanced frequency and absolute number of peritoneal B2 cells
• mice show a rescue of the defect in B-cell maturation, with increased splenic mature B cells, particularly the MZ B cells
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• mice exhibit normal numbers of B cells in the spleen
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• LPS-induced
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• LPS-induced
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• LPS-induced
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• reduction in peripheral B cell numbers
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• reduction in peripheral B cell numbers
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• severely decreased numbers of marginal zone B cells in spleen
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• increased numbers of follicular B cells in spleen
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• severely decreased numbers of marginal zone B cells in spleen
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• increased numbers of follicular B cells in spleen
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• decreased numbers of follicular B cells in spleen
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• increased numbers of marginal zone B cells in spleen
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• decreased numbers of follicular B cells in spleen
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• increased numbers of marginal zone B cells in spleen
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• severely reduced numbers of splenic B cells in the T1(Cd21loCd24hi) and T2 (Cd21hiCd24hi) stages
• B220+ cells markedly reduced, particularly in the follicular regions of the spleen
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• reduced numbers of Cd21intCd24lo cells
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• reduced numbers of Cd21hiCd23lo cells
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• reduced follicular region size
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• severely reduced numbers of splenic B cells in the T1(Cd21loCd24hi) and T2 (Cd21hiCd24hi) stages
• B220+ cells markedly reduced, particularly in the follicular regions of the spleen
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• reduced numbers of Cd21intCd24lo cells
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• reduced numbers of Cd21hiCd23lo cells
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• reduced follicular region size
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• decrease in the number of T2 B cells
• almost complete absence of CD1d
T2 B cells, the precursors of marginal zone B cells (pre-MZB)
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• complete absence of the perifollicular rim consisting of IgMhiIgDlo cells in the spleen
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• near complete absence of marginal zone B cells in the spleen
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• decrease in the number of T2 B cells
• almost complete absence of CD1d
T2 B cells, the precursors of marginal zone B cells (pre-MZB)
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• complete absence of the perifollicular rim consisting of IgMhiIgDlo cells in the spleen
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• near complete absence of marginal zone B cells in the spleen
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• B cell proliferation is slightly impaired in response to CD40/CD50 stimulation but not in response to LPS stimulation
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• decrease in the memory B cell population
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• decrease in the germinal center B cell population
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• germinal center formation is delayed in response to T cell dependent antigen stimulation
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• after antigen stimulation increased apoptosis is seen in germinal center B cells
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• antibody response (IgG1) to NP25-BSA is markedly reduced with the decrease occurring because of a decrease in the germinal center B cell and memory B cell populations
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• B cell proliferation is slightly impaired in response to CD40/CD50 stimulation but not in response to LPS stimulation
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• decrease in the memory B cell population
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• decrease in the germinal center B cell population
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• germinal center formation is delayed in response to T cell dependent antigen stimulation
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• after antigen stimulation increased apoptosis is seen in germinal center B cells
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• antibody response (IgG1) to NP25-BSA is markedly reduced with the decrease occurring because of a decrease in the germinal center B cell and memory B cell populations
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• B cell proliferation is slightly impaired in response to CD40/CD50 stimulation but not in response to LPS stimulation
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• numbers of marginal zone B cells in the spleen are 1/6 to 1/4 of those in the control mice
• IgM+IgD- marginal zone B cells are reduced in the spleen
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• numbers of marginal zone B cells in the spleen are 1/6 to 1/4 of those in the control mice
• IgM+IgD- marginal zone B cells are reduced in the spleen
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• similar to mice with recombination only in T cells
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• similar to mice with recombination only in T cells
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• similar to mice with recombination only in T cells
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• similar to mice with recombination only in T cells
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• similar to mice with recombination only in T cells
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• similar to mice with recombination only in T cells
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• mice exhibit normal B and T cell development, immunoglobulin class-switch recombination and genomic stability in dividing B lymphocytes
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• pre-immune IgG in the serum
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• anti-NP27 IgG1 following immunization
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• pre-immune IgG in the serum
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• anti-NP27 IgG1 following immunization
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• with B cell blasts outnumbering normal splenic B cells 20-fold in tamoxifen-treated mice
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• CD19+ B cells in tamoxifen-treated mice
• B cell blasts outnumbering normal splenic B cells 20-fold in tamoxifen-treated mice
• however, cell counts return to baseline after 2 weeks and a second application of tamoxifen does not result in another wave of B cell expansion
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• massive expansion in tamoxifen-treated mice
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• massive expansion in tamoxifen-treated mice
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• in tamoxifen-treated mice
• however, T cell numbers decrease 8 days after tamoxifen application
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• vigorous degranulation when T cells from tamoxifen-treated mice are exposed to LMP1-transduced B cells in vitro
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• with B cell blasts outnumbering normal splenic B cells 20-fold in tamoxifen-treated mice
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• CD19+ B cells in tamoxifen-treated mice
• B cell blasts outnumbering normal splenic B cells 20-fold in tamoxifen-treated mice
• however, cell counts return to baseline after 2 weeks and a second application of tamoxifen does not result in another wave of B cell expansion
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• massive expansion in tamoxifen-treated mice
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• massive expansion in tamoxifen-treated mice
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• in tamoxifen-treated mice
• however, T cell numbers decrease 8 days after tamoxifen application
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• vigorous degranulation when T cells from tamoxifen-treated mice are exposed to LMP1-transduced B cells in vitro
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• with B cell blasts outnumbering normal splenic B cells 20-fold in tamoxifen-treated mice
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• large immunoblasts with irregularly shaped nuclei and moderate cytoplasm in lymphoid and other tissues such as kidney and liver when immunized periodically
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• increased number of B220- cells, expressing more CD138 when immunized periodically
• the few remaining B220+ cells mostly (pre)memory B cells (MBs) and not germinal center B cells (GCBs) when immunized periodically
• normal mature B cell numbers in bone marrow when immunized periodically
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• large immunoblasts with irregularly shaped nuclei and moderate cytoplasm mostly outside follicles in red pulp when immunized periodically
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• large immunoblasts with irregularly shaped nuclei and moderate cytoplasm in lymphoid and other tissues such as kidney and liver when immunized periodically
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• increased number of B220- cells, expressing more CD138 when immunized periodically
• the few remaining B220+ cells mostly (pre)memory B cells (MBs) and not germinal center B cells (GCBs) when immunized periodically
• normal mature B cell numbers in bone marrow when immunized periodically
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• large immunoblasts with irregularly shaped nuclei and moderate cytoplasm mostly outside follicles in red pulp when immunized periodically
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• when immunized periodically
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• in kidney, lung, liver, intestines and other organs when immunized periodically
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• 5-fold enlargement
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• 17-fold enlargement in the lymph nodes
• weight of the enlarged lymph nodes is still 200- to 300-fold less than in Fastm1.1Cgn Faslpr trans-heterozygous mice
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• 5-fold enlargement
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• 5-fold enlargement
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• 15x increase in spleen 10 days after tamoxifen tre
• persistently high number of IgM+ plasma cells in spleen and bone marrow for at least 70 weeks after tamoxifen treatment
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• high total IgM serum levels for at least 70 weeks after tamoxifen treatment, displaying discrete paraprotein bands in the gamma-globulin zone upon serum protein electrophoresis
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• 15x increase in spleen 10 days after tamoxifen tre
• persistently high number of IgM+ plasma cells in spleen and bone marrow for at least 70 weeks after tamoxifen treatment
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• high total IgM serum levels for at least 70 weeks after tamoxifen treatment, displaying discrete paraprotein bands in the gamma-globulin zone upon serum protein electrophoresis
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
monoclonal gammopathy of uncertain significance | DOID:7442 | J:308792 |
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• mice exhibit no differences in spleen or lymph node size or in the numbers or phenotype of the B cells within these peripheral lymphoid tissues compared with wild-type mice
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• in response to CD40L, mice exhibit 10-fold lower germinal center B cells compared with wild-type mice
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• in the lymph nodes, follicular, and marginal zone
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• in response to CD40L
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• in response to CD40L, mice exhibit 10-fold lower germinal center B cells compared with wild-type mice
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• in the lymph nodes, follicular, and marginal zone
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• in response to CD40L
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• mice exhibit normal B cell development in the spleen and lymph node unlike in Tnfrsf13ctm1Mass homozygotes
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• due to expansion of B cells, regulatory T cells, CD4 and CD8 effector-like T cell, and eosinophils
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• in the spleen
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• in the spleen
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• in the spleen
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• mice exhibit an increase in CD4 and CD8 effector-like T cells in the spleen compared with control mice
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• due to expansion of B cells, regulatory T cells, CD4 and CD8 effector-like T cell, and eosinophils
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• in the spleen
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• in the spleen
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• in the spleen
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• mice exhibit an increase in CD4 and CD8 effector-like T cells in the spleen compared with control mice
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• due to expansion of B cells, regulatory T cells, CD4 and CD8 effector-like T cell, and eosinophils
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• there are greatly increased numbers of marginal zone B cells in both spleen and lymph nodes
• surface expression of CD21 on these cells is enhanced
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• 50% of B cells remain viable in unsupplemented culture for up to 10 days compared to no survival of wild-type cells
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• there are greatly increased numbers of marginal zone B cells in both spleen and lymph nodes
• surface expression of CD21 on these cells is enhanced
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• 50% of B cells remain viable in unsupplemented culture for up to 10 days compared to no survival of wild-type cells
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• there is almost a 2-fold increase in the number of follicular B cells found in the spleen
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• there are greatly increased numbers of marginal zone B cells in both spleen and lymph nodes
• surface expression of CD21 on these cells is enhanced
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• 50% of B cells remain viable in unsupplemented culture for up to 10 days compared to no survival of wild-type cells
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• there is almost a 2-fold increase in the number of follicular B cells found in the spleen
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• there are greatly increased numbers of marginal zone B cells in both spleen and lymph nodes
• surface expression of CD21 on these cells is enhanced
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• 50% of B cells remain viable in unsupplemented culture for up to 10 days compared to no survival of wild-type cells
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• in the bone marrow, pro-B and re-circulating B cell numbers are decreased by half compared to in wild-type mice
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• in the bone marrow, total B cell number in the bone marrow is reduced to 30% of wild-type
• the spleen contains half the number of B cells as in wild-type mice
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• in the bone marrow, immature B cells are decreased to 18% of wild-type numbers
• in the spleen, immature B cells are reduced by 50% compared to in wild-type mice
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• in the spleen, transitional B cells are reduced by 50% compared to in wild-type mice
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• in the spleen, mature B cells are reduced by 50% compared to in wild-type mice
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• in the bone marrow, pre-B cells are decreased to 18% of wild-type numbers
• GFP+ pre-B cells are absent in the bone marrow
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• in the bone marrow, pro-B and re-circulating B cell numbers are decreased by half compared to in wild-type mice
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• in the bone marrow, total B cell number in the bone marrow is reduced to 30% of wild-type
• the spleen contains half the number of B cells as in wild-type mice
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• in the bone marrow, immature B cells are decreased to 18% of wild-type numbers
• in the spleen, immature B cells are reduced by 50% compared to in wild-type mice
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• in the spleen, transitional B cells are reduced by 50% compared to in wild-type mice
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• in the spleen, mature B cells are reduced by 50% compared to in wild-type mice
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• in the bone marrow, pre-B cells are decreased to 18% of wild-type numbers
• GFP+ pre-B cells are absent in the bone marrow
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• in response to LPS or anti-CD40 stimulation
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• in response to LPS or anti-CD40 stimulation
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• in response to LPS or anti-CD40 stimulation
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• almost complete loss
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• almost complete loss
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• mice exhibit normal B cell development
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• B cells prime MOG-specific 2D2 TCR transgenic CD4 T cell proliferation to a lesser extent than wild-type cells
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• bone marrow-derived dendritic cells fail to generate an antigen-specific response unlike wild-type cells
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• resistant in a passive or active model
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• B cells prime MOG-specific 2D2 TCR transgenic CD4 T cell proliferation to a lesser extent than wild-type cells
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• mutant mice are viable and exhibit no hematopoietic defects, with normal bone marrow, spleen and thymus cell counts
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N |
• normal T and B lymphoid development
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|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• decrease in survival of B cells
|
• reduction in populations of some peripheral B cell subsets, particularly the lymph node compartment
• B cell generation is not impaired
|
• reduced number of peritoneal B-1 cells
|
• mutants fail to mount effective antibody responses to T cell-dependent and independent antigens
|
• hypoproliferation in response to anti-IgM, LPS, and anti-Tnfrsf5 (anti9-CD40)
|
• decrease in basal IgG levels
|
• decrease in basal IgM levels
|
• decrease in survival of B cells
|
• reduction in populations of some peripheral B cell subsets, particularly the lymph node compartment
• B cell generation is not impaired
|
• reduced number of peritoneal B-1 cells
|
• mutants fail to mount effective antibody responses to T cell-dependent and independent antigens
|
• hypoproliferation in response to anti-IgM, LPS, and anti-Tnfrsf5 (anti9-CD40)
|
• decrease in basal IgG levels
|
• decrease in basal IgM levels
|
• decrease in survival of B cells
|
• hypoproliferation in response to anti-IgM, LPS, and anti-Tnfrsf5 (anti9-CD40)
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• all mice die by prematurely, but female mice exhibit a shorter life span than male mice (median survival of 29 weeks for females compared with 43 weeks for males)
• Background Sensitivity: mice have a shorter life span than mice on a mixed background containing C57BL/6
|
• mice exhibit paravascular cell infiltration and thickening of the artery walls unlike in wild-type mice
|
• at 4 to 6 months
|
• mature B cells in aged mice lack CD23 expression unlike in wild-type mice indicating an age-dependent loss of part of the normal B cell differentiation program
|
• fewer transitional B cells with the AA4.1+ phenotype are detected compared to in wild-type mice
• however, the number of total transitional B cells is normal
|
• the number of activated B cells in the spleen is more than in wild-type mice
|
• in the spleen
|
• decreased in number
|
• in some mice
|
• following ovalbumin immunization, the memory response upon boosting with ovalbumin is 3-fold less than in similarly treated wild-type mice
|
• following IgM stimulation, apoptosis of transitional B cells is greater than in wild-type mice
• however, mature B cells exhibit normal apoptosis rates
|
• in response to BCR engagement by anti-IgM, B cell proliferation is less than in wild-type mice
• however, B cells exhibit normal proliferation in response to LPS, IL4, anti-CD40 and ODN1668, and IgM proliferation can be restored by co-stimulation with anto-CD40 or IL4
|
• prior to ovalbumin immunization, mice exhibit 3-fold more ovalbumin-specific immunoglobins compared to in wild-type mice
• however, the humoral response 14 days after immunization is normal
|
• 1.6-fold at 10 months of age
|
• 3.7-fold
|
• Background Sensitivity: mice develop systemic lupus erythematosus symptoms earlier in life than when mice are on a mixed background containing FVB/N
|
• interstitial
|
• interstitial
|
• glomeruli are enlarged and often filled with homogeneous protein deposits in the kidney, spleen, liver, and lungs unlike in wild-type mice
|
• mice exhibit paravascular cell infiltration and thickening of the artery walls unlike in wild-type mice
|
• following IgM stimulation, apoptosis of transitional B cells is greater than in wild-type mice
• however, mature B cells exhibit normal apoptosis rates
|
• in response to BCR engagement by anti-IgM, B cell proliferation is less than in wild-type mice
• however, B cells exhibit normal proliferation in response to LPS, IL4, anti-CD40 and ODN1668, and IgM proliferation can be restored by co-stimulation with anto-CD40 or IL4
|
• at 4 to 6 months
|
• mature B cells in aged mice lack CD23 expression unlike in wild-type mice indicating an age-dependent loss of part of the normal B cell differentiation program
|
• fewer transitional B cells with the AA4.1+ phenotype are detected compared to in wild-type mice
• however, the number of total transitional B cells is normal
|
• with islands of granulopoiesis
|
• 4- to 20-fold in the spleen
|
• the number of activated B cells in the spleen is more than in wild-type mice
|
• in the spleen
|
• decreased in number
|
• 1.6-fold at 10 months of age
|
• 3.7-fold
|
• following IgM stimulation, apoptosis of transitional B cells is greater than in wild-type mice
• however, mature B cells exhibit normal apoptosis rates
|
• in response to BCR engagement by anti-IgM, B cell proliferation is less than in wild-type mice
• however, B cells exhibit normal proliferation in response to LPS, IL4, anti-CD40 and ODN1668, and IgM proliferation can be restored by co-stimulation with anto-CD40 or IL4
|
• at 4 to 6 months
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
systemic lupus erythematosus | DOID:9074 |
OMIM:152700 OMIM:300809 OMIM:605480 OMIM:608437 OMIM:609903 OMIM:609939 OMIM:610065 OMIM:610066 OMIM:612254 OMIM:612378 OMIM:613145 OMIM:614420 |
J:147840 |
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• Background Sensitivity: mice have a longer life span than mice on a mixed background containing C57BL/6
• all mice die prematurely, but female mice exhibit a shorter life span than male mice (median survival of 73 weeks for females compared with over 90 weeks for males)
|
• Background Sensitivity: mice develop systemic lupus erythematosus symptoms later in life than when mice are on a mixed background containing C57BL/6
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• no significant increase in the production of IgA+ compared to mice homozygous for Map3k14tm1Rds alone
|
• unlike mutant mice wild-type for Map3k14 the serum titer of IgA is not elevated
|
• no significant increase in the production of IgA+ compared to mice homozygous for Map3k14tm1Rds alone
|
• unlike mutant mice wild-type for Map3k14 the serum titer of IgA is not elevated
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• much greater frequency of IgA+ B cells in mesenteric lymph nodes and Peyer's patches compared to age matched controls
• significantly greater frequency and number of IgA+ B cells in the spleen in young mice immunized with a T cell dependent antigen
|
• moderate increase in NKKB activation following induction
|
• expression analysis indicates a defect in the negative regulation of class switching to IgA
|
• production of antigen specific IgA in immunized mice is enhanced compared to similarly treated controls
• starting at 12 weeks of age serum IgA levels are increased in unimmunized mice compared to aged match controls
|
• production of antigen specific IgM in immunized mice is moderately enhanced compared to similarly treated controls
|
• higher serum titers of the autoantibody antinuclear antigen at 8 months of age
|
• at 8 months of age
|
• at 8 months of age
|
• prominent deposition of antibodies in the kidney glomeruli at 8 months of age a sign of nephropathy
|
• at 8 months of age
|
• at 8 months of age
|
• at 8 months of age
|
• much greater frequency of IgA+ B cells in mesenteric lymph nodes and Peyer's patches compared to age matched controls
• significantly greater frequency and number of IgA+ B cells in the spleen in young mice immunized with a T cell dependent antigen
|
• moderate increase in NKKB activation following induction
|
• expression analysis indicates a defect in the negative regulation of class switching to IgA
|
• production of antigen specific IgA in immunized mice is enhanced compared to similarly treated controls
• starting at 12 weeks of age serum IgA levels are increased in unimmunized mice compared to aged match controls
|
• production of antigen specific IgM in immunized mice is moderately enhanced compared to similarly treated controls
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• transient expansion of B cells in absence or presence of added mitogens in vitro
|
• transient expansion of B cells in absence or presence of added mitogens in vitro
|
• transient expansion of B cells in absence or presence of added mitogens in vitro
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• normal B cell development in bone marrow
• normal Ig class switching in B cells in spleen, mesenteric lymph nodes and Peyers patches
|
• from age 30 weeks
|
• increased frequency and number from age 30 weeks, increasing over time
|
• increased number of IgM+ plasma cells
• increased plasma cell compartment in spleen and bone marrow
• increased frequency and number of TACI+ CD138+ plasma cells from age 50 weeks
|
• increased frequency and number of germinal center B cells from age 30 weeks, increasing over time
• normal frequency of follicular and marginal zone B cells
|
• increased serum levels from age 10 weeks, increasing over time
|
• from age 30 weeks
|
• increased frequency and number from age 30 weeks, increasing over time
|
• increased number of IgM+ plasma cells
• increased plasma cell compartment in spleen and bone marrow
• increased frequency and number of TACI+ CD138+ plasma cells from age 50 weeks
|
• increased frequency and number of germinal center B cells from age 30 weeks, increasing over time
• normal frequency of follicular and marginal zone B cells
|
• increased serum levels from age 10 weeks, increasing over time
|
• from age 30 weeks
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• in the spleen and lymph node
|
• in the spleen and lymph node
|
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 03/25/2025 MGI 6.24 |
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