Regulation of BCR signal transduction in B-1 cells requires the expression of the Src family kinase Lck.
Although found predominantly in the peritoneal and pleural cavities, B-1 cells are also present in other peripheral tissues such as spleen and lung. While similar in surface phenotypes, such as CD5, all B-1 cells are not equivalent in their response to stimuli. Here, we report that the src family kinase Lck is required to confer the BCR hyporesponsiveness typical of CD5+ B-1 cells and appears involved in the maintenance of their unique function. Splenic B-1 cells express CD5 but not Lck and are not hyporesponsive; however, within the peritoneum, these B-1 cells are induced to express Lck and acquire a hyporesponsive phenotype. Peritoneal B-1 cells from lck-deficient mice, while CD5+, no longer exhibit attenuated BCR signaling. Interestingly, lck-null mice exhibited increased natural antibody levels characteristic of B-1 cells. Taken together, these results demonstrate a key role for Lck in modulating the signaling and cellular fate of B-1 B cells.
Dal Porto
Joseph M
JM
Integrated Department of Immunology, National Jewish Medical and Research Center, University of Colorado School of Medicine, Denver 80206, USA.
Burke
Kathy
K
Cambier
John C
JC
D019264:Adoptive Transfer; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D018956:CD5 Antigens / Q000276:immunology; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015151:Immunoblotting; D007070:Immunoglobulin A / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010537:Peritoneum / Q000166:cytology / Q000276:immunology; D011233:Precipitin Tests; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology
D018956:CD5 Antigens; D007070:Immunoglobulin A; D007075:Immunoglobulin M; D011947:Receptors, Antigen, B-Cell; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)