Negative signaling via Fc gamma RIIB1 in B cells blocks phospholipase C gamma 2 tyrosine phosphorylation but not Syk or Lyn activation

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 C gamma 2 (PLC gamma 2) 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 PLC gamma 2 hut not in activation of the upstream kinases, Syk and Lyn, under co-crosslinking conditions. We conclude that the negative signal acts directly on PLC gamma 2 and is consistent with recent studies describing an activation-induced association of a phosphotyrosine phosphatase with tyrosine-phosphorylated B cell Fc receptor.