International Immunology Advance Access originally published online on February 19, 2009
International Immunology 2009 21(4):403-414; doi:10.1093/intimm/dxp006
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c-Abl-deficient mice exhibit reduced numbers of peritoneal B-1 cells and defects in BCR-induced B cell activation
1 Integrated Program in Cellular, Molecular, Structural and Genetic Studies
2 Department of Biochemistry and Molecular Biophysics, College of Physicians and Surgeons, Columbia University, New York, NY, USA
3 Howard Hughes Medical Institute, New York, NY, USA
Correspondence to: S. P. Goff; E-mail: goff{at}cancercenter.columbia.edu
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.
Keywords: co-stimulation, protein kinases, transgenic/knockout mice
Transmitting editor: W. Yokoyama
Received 25 September 2008, accepted 16 January 2009.