Phenotypes Associated with This Genotype

Genotype
MGI:3609010

• Allelic Composition: Spi1^tm1Sing/Spi1⁺; Spib^tm1Mcs/Spib^tm1Mcs
• Genetic Background: involves: 129S/SvEv * 129X1/SvJ

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

hematopoietic system

increased B cell apoptosis ( J:88257 )

• B220⁺ TUNEL<+> splenic lymphocytes are increased 4 times over normal levels

• Annexin A5^hi immature and mature B cells are increased 3 to 4 times over normal levels

• increased splenic B cell apoptosis is found after immunization with the T-dependent antigen DNP-KLH

decreased B cell proliferation ( J:88257 )

• defect in proliferation in response to anti-IgM stimulation is much more severe than in Sfpi1^tm1Sing wild-type Spib^tm1Mcs homozygotes

• 2 to 3 fold reduction in B cell response to LPS although response to PMA and ionomycin is normal and response to anti-CD40 and IL4 is normal

• IgM cross-linking or pervanadate/H₂0₂ stimulation yields less than normal levels of tyrosine phosphorylation and IgM cross-linking also yields less calcium mobilization than normal

• normal levels of LYN, FYN, BLK, SYK, and BTK are found and in vitro kinase assays of enolase show normal kinase activity in B cells and BLNK, VAV, CD79A, and CD79B are expressed at normal levels with SYK co-precipitating with CD79, but tyrosine phosphorylation of BLNK and PLC gamma is decreased

abnormal B cell differentiation ( J:88257 )

abnormal immature B cell morphology ( J:88257 )

• decreased bone marrow B220^hi/int CD43^- IgM⁺ and B220^hi CD43^- HSA^lo B cells and normal B220^int CD43^- IgM^- and B220^hi CD43^- HSA^hi population indicating a deficiency in immature and mature B cells but normal levels of pro-B and pre-B cells

• E16.5 fetal liver has reduced numbers of B220⁺ CD43^- cells but normal numbers of B220⁺ CD43⁺ cells

• bone marrow has 50% fewer IgM⁺ IgD⁺ and IgM⁺ IgD^- B cells, and also decreased B220⁺ CD43^- B cells and B220⁺ BP-1⁺ B cells

• although B cells from bone marrow and periphery have normal Igl and Igk expression, splenic B cells have 2 to 4 fold higher surface expression of IgM and B cells also express high levels of surface CD19 and CD21

decreased B cell number ( J:88257 )

• B220⁺ IgM⁺ and IgM⁺ IgD⁺ B cells are decreased in number by 50% in spleen and 60%-80% in lymph node

• total numbers of B cells is reduced

absent spleen germinal center ( J:88257 )

• no peanut agglutinin positive germinal centers are found at 10 or 28 days post-immunization

immune system

immune system phenotype ( J:88257 )

N • myeloid lineages appear normal by flow cytometry

N • thymic CD4/CD8 profiles and splenic CD4/CD8 and TCRab/CD3 profiles are normal

increased B cell apoptosis ( J:88257 )

• B220⁺ TUNEL<+> splenic lymphocytes are increased 4 times over normal levels

• Annexin A5^hi immature and mature B cells are increased 3 to 4 times over normal levels

• increased splenic B cell apoptosis is found after immunization with the T-dependent antigen DNP-KLH

decreased B cell proliferation ( J:88257 )

• defect in proliferation in response to anti-IgM stimulation is much more severe than in Sfpi1^tm1Sing wild-type Spib^tm1Mcs homozygotes

• 2 to 3 fold reduction in B cell response to LPS although response to PMA and ionomycin is normal and response to anti-CD40 and IL4 is normal

• IgM cross-linking or pervanadate/H₂0₂ stimulation yields less than normal levels of tyrosine phosphorylation and IgM cross-linking also yields less calcium mobilization than normal

• normal levels of LYN, FYN, BLK, SYK, and BTK are found and in vitro kinase assays of enolase show normal kinase activity in B cells and BLNK, VAV, CD79A, and CD79B are expressed at normal levels with SYK co-precipitating with CD79, but tyrosine phosphorylation of BLNK and PLC gamma is decreased

abnormal B cell differentiation ( J:88257 )

abnormal immature B cell morphology ( J:88257 )

• decreased bone marrow B220^hi/int CD43^- IgM⁺ and B220^hi CD43^- HSA^lo B cells and normal B220^int CD43^- IgM^- and B220^hi CD43^- HSA^hi population indicating a deficiency in immature and mature B cells but normal levels of pro-B and pre-B cells

• E16.5 fetal liver has reduced numbers of B220⁺ CD43^- cells but normal numbers of B220⁺ CD43⁺ cells

• bone marrow has 50% fewer IgM⁺ IgD⁺ and IgM⁺ IgD^- B cells, and also decreased B220⁺ CD43^- B cells and B220⁺ BP-1⁺ B cells

• although B cells from bone marrow and periphery have normal Igl and Igk expression, splenic B cells have 2 to 4 fold higher surface expression of IgM and B cells also express high levels of surface CD19 and CD21

decreased B cell number ( J:88257 )

• B220⁺ IgM⁺ and IgM⁺ IgD⁺ B cells are decreased in number by 50% in spleen and 60%-80% in lymph node

• total numbers of B cells is reduced

absent spleen germinal center ( J:88257 )

• no peanut agglutinin positive germinal centers are found at 10 or 28 days post-immunization

cellular

increased B cell apoptosis ( J:88257 )

• B220⁺ TUNEL<+> splenic lymphocytes are increased 4 times over normal levels

• Annexin A5^hi immature and mature B cells are increased 3 to 4 times over normal levels

• increased splenic B cell apoptosis is found after immunization with the T-dependent antigen DNP-KLH

decreased B cell proliferation ( J:88257 )

• defect in proliferation in response to anti-IgM stimulation is much more severe than in Sfpi1^tm1Sing wild-type Spib^tm1Mcs homozygotes

• 2 to 3 fold reduction in B cell response to LPS although response to PMA and ionomycin is normal and response to anti-CD40 and IL4 is normal

• IgM cross-linking or pervanadate/H₂0₂ stimulation yields less than normal levels of tyrosine phosphorylation and IgM cross-linking also yields less calcium mobilization than normal

• normal levels of LYN, FYN, BLK, SYK, and BTK are found and in vitro kinase assays of enolase show normal kinase activity in B cells and BLNK, VAV, CD79A, and CD79B are expressed at normal levels with SYK co-precipitating with CD79, but tyrosine phosphorylation of BLNK and PLC gamma is decreased