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

Immunity. 2000 Aug;13(2):277-85. doi: 10.1016/s1074-7613(00)00027-3.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, CD / genetics*
  • Antigens, CD / immunology
  • Autoimmune Diseases / genetics*
  • Autoimmune Diseases / immunology
  • B-Lymphocytes / immunology*
  • Epistasis, Genetic
  • Gene Deletion
  • Genetic Predisposition to Disease
  • Mice
  • Receptors, IgG / genetics*
  • Receptors, IgG / immunology
  • Species Specificity

Substances

  • Antigens, CD
  • Fc gamma receptor IIB
  • Receptors, IgG