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

CD5, a membrane-associated glycoprotein, has been shown to negatively regul ate 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 si gnals 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 c ytosolic protein tyrosine phosphatase, has also been implicated in the nega tive regulation of antigen receptor-mediated signaling. The present study s hows that SHP-1 is constitutively associated with the BCR in B-1 cells. Thi s association is mediated in part by CD5, as it is reduced substantially af ter 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 c ross-linking of CD5 also restores a normal calcium mobilization response as well as NF-kappa B activation in B-1 cells. These data support a model whe reby CD5 negatively regulates antigen receptor-mediated growth signals by r ecruiting SHP-1 into the BCR complex in B-1 cells.