Role of the inositol phosphatase SHIP in negative regulation of the immune system by the receptor Fc gamma RIIB

IMMUNE complexes are potent activators of inflammatory cells, triggering effector responses through the crosslinking of Fc receptors (FcRs) such as Fc epsilon RI or Fc gamma RIII (ref, 1). On B cells and mast cells, immune complexes are also negative regulators of activation triggered by antigen and Fc receptors, a consequence of coligation of the B-cell antigen receptor or Fc epsilon RI, respectively, and the inhibitory receptor Fc gamma RIIB. Here we show that inhibitory signalling by Fc gamma RIIB does not require the SH2-domain-containing protein tyrosine phosphatase, SHP-1, in mast cells and results in the recruitment of the SH2-domain-containing inositol polyphosphate 5-phosphatase, SHIP, to the tyrosine-phosphorylated 13-amino-acid inhibitory motif of Fc gamma RIIB in both B cells and mast cells. SHIP, by hydrolysing the 5-phosphate of phosphatidylinositol(3,4,5)P-3 and inositol(1,3,4,5) P-4, suggests a mechanism by which Fc gamma RIIB can inhibit calcium influx and downstream responses triggered by immune receptors.