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

Goutam Sen, Gabriel Bikah, Chandrasekar Venkataraman, Subbarao Bondada

Research output: Contribution to journalArticlepeer-review

100 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)3319-3328
Number of pages10
JournalEuropean Journal of Immunology
Volume29
Issue number10
DOIs
StatePublished - 1999

Keywords

  • Autoantibody
  • B cell receptor
  • Calcium
  • NF-κβ
  • Peritoneal B cell

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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