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

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.

• Authors: S Bolland, J V Ravetch
• Journal: Immunity (Immunity) Vol. 13 Issue 2 Pg. 277-85 (Aug 2000) ISSN: 1074-7613 [Print] United States
• PMID: 10981970 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

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

Topics

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