CD22 IS BOTH A POSITIVE AND NEGATIVE REGULATOR OF B-LYMPHOCYTE ANTIGEN RECEPTOR SIGNAL-TRANSDUCTION - ALTERED SIGNALING IN CD22-DEFICIENT MICE

B cell activation following antigen receptor cross-linking can be augm ented in vitro by ligation of cell surface CD22, which associates with the SHP1 protein tyrosine phosphatase. The targeted deletion of CD22 in mice demonstrated that CD22 differentially regulates antigen recept or signaling in resting and antigen-stimulated B lymphocytes. a cells from CD22-deficient mice exhibited the cell surface phenotype and augm ented intracellular calcium responses characteristic of chronically st imulated B cells, as occurs in SHP1-defective mice. Thus, CD22 negativ ely regulates antigen receptor signaling in the absence of antigen. Ho wever, activation of CD22-deficient B lymphocytes by prolonged IgM cro ss-linking resulted in modest B cell proliferation, demonstrating that CD22 positively regulates antigen receptor signaling in the presence of antigen.