A subset of B lymphocytes present primarily in the peritoneal and pleural cavities is defined by the expression of CD5 and is elevated in autoimmune diseases. Upon signaling through membrane immunoglobulin M (mIgM), splenic B lymphocytes (B-2) proliferate, whereas peritoneal B cells (B-1) undergo apoptosis. However, in CD5-deficient mice, B-1 cells responded to mIgM crosslinking by developing a resistance to apoptosis and entering the cell cycle. In wild-type B-1 cells, prevention of association between CD5 and mIgM rescued their growth response to mIgM crosslinking. Thus the B cell receptor-mediated signaling is negatively regulated by CD5 in normal B-1 cells.
CD5 is a glycoprotein expressed at a high level on the surface of mature T lymphocytes. Studies with CD5 mAb and CD5-deficient mice have shown that the CD5 molecules have a significant role in T cell growth response. However, the precise role of CD5 in immune cell interactions is still unclear. The present study provides evidence that CD5 plays a direct role in providing growth signals during the contact-dependent activation and proliferation of splenic B cells. An anti-CD5 mAb inhibited Th1- and Th2-type cell-induced B cell proliferation. CD5-Ig, a chimeric fusion protein, induced proliferation of resting B cells. Flow cytometric analyses using CD5-Ig and mAb to CD72 demonstrated that CD5 bound to a ligand (CD5L), and this binding was not blocked by a variety of anti-CD72 mAb. Also, CD5-Ig did not bind to CD72+-transfected cells. Immunoprecipitation of surface labeled B cell molecules with CD5-Ig showed that CD5L was composed of 77-80 and 38-40 kDa polypeptide chains, distinct from CD72. CD5L was expressed on activated splenic B cells, but not T cells, whereas its expression was constitutive on peritoneal B cells and on B lymphoma cell lines.
CD5, a membrane-associated glycoprotein, has been shown to negatively regulate antigen receptor-mediated growth responses in peritoneal B lymphocytes, thymocytes and mature T cells. The CD5-expressing peritoneal B cells (B-1) that are normally unresponsive to B cell receptor (BCR)-mediated growth signals mount a proliferative response to BCR cross-linking if the CD5 gene is deleted or if the CD5 molecule is sequestered away from the BCR. SHP-1, a cytosolic protein tyrosine phosphatase, has also been implicated in the negative regulation of antigen receptor-mediated signaling. The present study shows that SHP-1 is constitutively associated with the BCR in B-1 cells. This association is mediated in part by CD5, as it is reduced substantially after antigen receptor ligation in CD5(-/-) B-1 cells, and upon sequestration of CD5 from the antigen receptor complexes in wild-type B-1 cells. Prior cross-linking of CD5 also restores a normal calcium mobilization response as well as NF-kappaB activation in B-1 cells. These data support a model whereby CD5 negatively regulates antigen receptor-mediated growth signals by recruiting SHP-1 into the BCR complex in B-1 cells.
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