Negative regulation of antigen receptor-mediated signaling by constitutive association of CD5 with the SHP-1 protein tyrosine phosphatase in B-1 B cells

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 crosslinking 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-κB 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.