Fc gamma RIIB1 inhibition of BCR-mediated phosphoinositide hydrolysis and Ca2+ mobilization is integrated by CD19 dephosphorylation

The B cell receptor for immunoglobulin G, Fc gamma RIIB1, is a potent transducer of signals that block antigen-induced B cell activation. Coligation of Fc gamma RIIB1 with B lymphocyte antigen receptors (BCR) causes premature termination of phosphoinositide hydrolysis and Ca2+ mobilization and inhibits proliferation. This inhibitory signal is mediated in part by phosphorylation of Fc gamma RIIB1 and recruitment of phosphatases; however, the molecular target(s) of effecters is unknown. Here we report that Fc gamma RIIB1 inhibition of BCR signaling is mediated in part by selective dephosphorylation of CD19, a BCR accessory molecule and coreceptor. CD19 dephosphorylation leads to failed CD19 association with phosphatidylinositol 3-kinase, and this in turn leads to termination of inositol-1,4,5-trisphosphate production, intracellular Ca2+ release, and Ca2+ influx. The results define a molecular circuit by which Fc gamma RIIB signals block phosphoinositide hydrolysis.