Negative Signaling via FcγRIIB1 in B Cells Blocks Phospholipase Cγ2 Tyrosine Phosphorylation but Not Syk or Lyn Activation

• Published in: The Journal of biological chemistry 1996-08, Vol.271 (33), p.20182-20186
• Main Authors: Sarkar, Sujata, Schlottmann, Klaus, Cooney, Damon, Coggeshall, K. Mark
• Format: Article
• Language: English
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.271.33.20182

Crosslinking of the B cell antigen receptor surface immunoglobulin induces tyrosine phosphorylation and activation of the Src family and Syk tyrosine protein kinases, tyrosine phosphorylation of phospholipase Cγ2 (PLCγ2) and increases in intracellular second messengers inositol phosphates and Ca2+. These activation events, in conjunction with other pathways, culminate in the induction of B cell proliferation and differentiation. In contrast, co-crosslinking surface Ig with the B cell IgG Fc receptor prevents many of these activation events, including B cell proliferation and differentiation. The precise nature of the negative signal(s) derived from Fc receptors that prevent B cell activation is not known. Here, early activation events were examined in B cells stimulated via the antigen receptor alone or under co-crosslinking conditions. The data indicated a selective block in the tyrosine phosphorylation and activation of PLCγ2 but not in activation of the upstream kinases, Syk and Lyn, under co-crosslinking conditions. We conclude that the negative signal acts directly on PLCγ2 and is consistent with recent studies describing an activation-induced association of a phosphotyrosine phosphatase with tyrosine-phosphorylated B cell Fc receptor.