SHIP recruitment attenuates FcγRIIB-induced B cell apoptosis

Fc gamma RIIB is an inhibitory receptor that terminates activation signals initiated by antigen cross-linking of the BCR through the recruitment of SHIP. Fc gamma RIIB can also signal independently of BCR coligation to directly mediate an apoptotic response, requiring only an intact transmembrane domain. Failure to recruit SHIP, either by deletion of SHIP or mutation of Fc gamma RIIB, results in enhanced Fc gamma RIIB-triggered apoptosis. Thus, in the germinal center, where ICs are retained by FDCs, Fc gamma RIIB may be an active determinant in the negative selection of B cells whose BCRs have reduced affinity for antigen as a result of somatic hypermutation. Selection of B cells may represent the sum of opposing signals generated by the interaction of ICs with the BCR and Fc gamma RIIB through pathways modulated by SHIP.