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, FcgammaRIIB can potentially determine the fate of B cells upon IgG immune complex engagement. We now provide evidence for FcgammaRIIB as a component of a peripheral tolerance pathway with the observation that RIIB-/- mice develop autoantibodies and autoimmune glomerulonephritis in a strain-dependent fashion. Transfer of the autoimmune phenotype is associated with the presence of donor RIIB-/- B cells, with the RIIB+/+ myeloid cells primarily derived from the recipient. These results suggest that deficiency of RIIB on B cells leads to autoimmune disease in specific genetic backgrounds, thus identifying it as a susceptibility factor under the influence of epistatic modifiers for the development of autoimmunity.
Bolland
S
S
Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, New York 10021, USA.
Ravetch
J V
JV
D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000276:immunology; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D004843:Epistasis, Genetic; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D051379:Mice; D017452:Receptors, IgG / Q000235:genetics* / Q000276:immunology; D013045:Species Specificity
D015703:Antigens, CD; C080571:Fc gamma receptor IIB; D017452:Receptors, IgG