Spontaneous autoimmune disease in Fc gamma RIIB-deficient mice results from strain-specific epistasis

By virtue of its ability to couple the BCR to an inhibitory pathway, Fc gam ma RIIB can potentially determine the fate of B cells upon IgG immune compl ex engagement. We now provide evidence for Fc gamma RIIB as a component of a peripheral tolerance pathway with the observation that RIIB-/- mice devel op autoantibodies and autoimmune glomerulonephritis in a strain-dependent f ashion. Transfer of the autoimmune phenotype is associated with the presenc e of donor RIIB-/- B cells, with the RIIB+/+ myeloid cells primarily derive d from the recipient. These results suggest that deficiency of RIIB on B ce lls leads to autoimmune disease in specific genetic backgrounds, thus ident ifying it as a susceptibility factor under the influence of epistatic modif iers for the development of autoimmunity.