FC-GAMMA-RIIB1 INHIBITION OF BCR-MEDIATED PHOSPHOINOSITIDE HYDROLYSISAND 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. Co ligation of Fc gamma RIIB1 with B lymphocyte antigen receptors (BCR) c auses premature termination of phosphoinositide hydrolysis and Ca2+ mo bilization and inhibits proliferation. This inhibitory signal is media ted in part by phosphorylation of Fc gamma RIIB1 and recruitment of ph osphatases; however, the molecular target(s) of effecters is unknown. Here we report that Fc gamma RIIB1 inhibition of BCR signaling is medi ated in part by selective dephosphorylation of CD19, a BCR accessory m olecule and coreceptor. CD19 dephosphorylation leads to failed CD19 as sociation with phosphatidylinositol 3-kinase, and this in turn leads t o termination of inositol-1,4,5-trisphosphate production, intracellula r Ca2+ release, and Ca2+ influx. The results define a molecular circui t by which Fc gamma RIIB signals block phosphoinositide hydrolysis.