c-Abl-deficient mice exhibit reduced numbers of peritoneal B-1 cells and defects in BCR-induced B cell activation.
A role for c-Abl in B cell development and signaling has been suggested by previous work showing that c-Abl-deficient mice have defects in bone marrow B cell development and that c-Abl-deficient B cells are hypoproliferative in response to antigen receptor stimulation. Here we show that in addition to defects in early B cell development, c-Abl-deficient mice have defects in peripheral B cell development, including reduced percentages of peritoneal B-1 cells as well as transitional and marginal zone B cells in the spleen. It has been shown that c-Abl kinase activity increases upon B cell receptor (BCR) stimulation and that one of the targets of tyrosine phosphorylation by c-Abl is CD19. However, the consequences of c-Abl activity on B cell activation and CD19 signaling remain unknown. Here, we show that c-Abl-deficient splenic B cells exhibit reduced calcium flux in response to CD19 cross-linking, consistent with a role for c-Abl in CD19-dependent signaling. Additionally, we show that c-Abl-deficient B cells are defective in their ability to be activated in response to antigen receptor engagement, suggesting a functional role for c-Abl in BCR-dependent activation signaling pathways.
Liberatore
Rachel A
RA
Columbia University, New York, NY, USA.
Goff
Stephen P
SP
D000818:Animals; D018941:Antigens, CD19 / Q000276:immunology* / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D002118:Calcium / Q000276:immunology / Q000378:metabolism; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009363:Neoplasm Proteins / Q000276:immunology / Q000378:metabolism; D010537:Peritoneum / Q000276:immunology*; D016315:Proto-Oncogene Proteins c-abl / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D020569:Proto-Oncogene Proteins c-rel / Q000276:immunology / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D051996:Transcription Factor RelA / Q000276:immunology / Q000378:metabolism
D018941:Antigens, CD19; D002352:Carrier Proteins; D009363:Neoplasm Proteins; D020569:Proto-Oncogene Proteins c-rel; D011947:Receptors, Antigen, B-Cell; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; D016315:Proto-Oncogene Proteins c-abl; D002118:Calcium