Phenotypes Associated with This Genotype

Genotype
MGI:4829791

• Allelic Composition: Cd19^tm1(cre)Cgn/Cd19⁺; Pten^tm1Hwu/Pten^tm1Hwu
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

hematopoietic system

abnormal B cell negative selection ( J:155314 )

• 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

increased B cell number ( J:83213 )

• increase in the absolute number of splenic B cells, attributed mainly to the expansion/accumulation of MZ B cells

increased B-1 B cell number ( J:83213 )

• expansion of the B1 cell population

increased marginal zone B cell number ( J:83213 )

• expansion of the MZ B cell compartment

abnormal plasma cell morphology ( J:114881 )

• increase in numbers of IgM^hi antibody secreting cells and decrease in numbers of IgG^hi antibody secreting cells

decreased spleen germinal center number ( J:83213 )

• reduction in germinal center formation in response to sheep red blood cell immunization and in response to environmental antigens

abnormal B cell physiology ( J:83213 )

• B cells are responsive to chemotactic stimuli but show reduced directed movement toward the stimulus

increased B cell apoptosis ( J:83213 )

• cultured B cells show increased apoptosis

increased B cell proliferation ( J:83213 , J:155314 )

• 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)

abnormal class switch recombination ( J:114881 )

• 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

decreased IgG level ( J:114881 )

• decrease in IgG after TNP-OVA immunization

increased IgM level ( J:114881 )

• increase in IgM after TNP-OVA immunization

immune system

abnormal B cell negative selection ( J:155314 )

• 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

increased B cell number ( J:83213 )

• increase in the absolute number of splenic B cells, attributed mainly to the expansion/accumulation of MZ B cells

increased B-1 B cell number ( J:83213 )

• expansion of the B1 cell population

increased marginal zone B cell number ( J:83213 )

• expansion of the MZ B cell compartment

abnormal plasma cell morphology ( J:114881 )

• increase in numbers of IgM^hi antibody secreting cells and decrease in numbers of IgG^hi antibody secreting cells

decreased spleen germinal center number ( J:83213 )

• reduction in germinal center formation in response to sheep red blood cell immunization and in response to environmental antigens

abnormal B cell physiology ( J:83213 )

• B cells are responsive to chemotactic stimuli but show reduced directed movement toward the stimulus

increased B cell apoptosis ( J:83213 )

• cultured B cells show increased apoptosis

increased B cell proliferation ( J:83213 , J:155314 )

• 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)

abnormal class switch recombination ( J:114881 )

• 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

decreased IgG level ( J:114881 )

• decrease in IgG after TNP-OVA immunization

increased IgM level ( J:114881 )

• increase in IgM after TNP-OVA immunization

cellular

increased B cell apoptosis ( J:83213 )

• cultured B cells show increased apoptosis

increased B cell proliferation ( J:83213 , J:155314 )

• 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)