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 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.
Sen
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Department of Microbiology and Immunology, Sanders Brown Center on Aging, University of Kentucky, Lexington 40536-0230, USA.
Bikah
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G
Venkataraman
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C
Bondada
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S
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000378:metabolism; D001402:B-Lymphocytes / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism*; D018956:CD5 Antigens / Q000276:immunology / Q000378:metabolism*; D002118:Calcium / Q000276:immunology / Q000378:metabolism; D002384:Catalysis; D007075:Immunoglobulin M / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D046911:Macromolecular Substances; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D010529:Peritoneal Cavity; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology*; D013997:Time Factors; D014443:Tyrosine / Q000378:metabolism
D000888:Antibodies, Anti-Idiotypic; D018956:CD5 Antigens; D007075:Immunoglobulin M; D047908:Intracellular Signaling Peptides and Proteins; D046911:Macromolecular Substances; D016328:NF-kappa B; D011947:Receptors, Antigen, B-Cell; C044203:anti-IgM; D014443:Tyrosine; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C509248:Ptpn6 protein, mouse; D002118:Calcium