IVIg-mediated amelioration of murine ITP via FcγRIIB is independent of SHIP1, SHP-1, and Btk activity

Abstract

Abstract It has been established that amelioration of murine immune thrombocytopenia purpura (ITP) by IVIg is dependent on the inhibitory receptor FcγRIIB. Co-cross-linking of the FcγRIIB with the B-cell receptor complex or with FcϵRI in mast cells results in cell inhibition, which is mediated by recruitment of the inositol phosphatase SHIP1 to the cytoplasmic tail of the FcγR. The FcγRIIB can also associate with protein tyrosine phosphatase SHP-1 as a potential secondary target of the receptor. Alternatively, homoaggregation of FcγRIIB can induce a proapoptotic state in B cells that is dependent on the presence of Bruton tyrosine kinase (Btk), a kinase also expressed in monocytes. We sought to determine if these signaling pathways may direct IVIg-mediated FcγRIIB-dependent regulation of in vivo monocyte function in a murine model of ITP in which IVIg functions in an FcγRIIB-dependent manner. We demonstrate that mice deficient in SHIP1, SHP-1, and Btk respond to the ameliorating effects of IVIg with the same kinetics as control mice. We conclude that IVIgmediated inhibitory pathways operating via monocyte FcγRIIB may involve a transmembrane signaling pathway different from that of B cells.