Abolition of anti-glomerular basement membrane antibody-mediated glomerulonephritis in FcR gamma-deficient mice

Several recent studies have demonstrated the central role of Fc receptors ( FcR) rather than the complement system in triggering hypersensitivity react ions. We investigated the role of FcR for IgG (Fc gamma R) using a murine m odel of accelerated anti-glomerular basement membrane (GBM) antibody-mediat ed glomerulonephritis as a representative of type II hypersensitivity disea ses. intravenous injection of rabbit anti-GBM antibody after preimmunizatio n with normal rabbit IgG induced proteinuria and azotemia in wild-type C57B L/6 and CD40(+/-) mice but not in FcR gamma chain (FcR gamma)(-/-) mice or CD40(-/-) mice. Light microscopic findings revealed marked tissue damage in the glomeruli of wild-type C57BL/6 and CD40(+/-) mice. However, no tissue damage except polymorphonuclear cell infiltration was observed in the glome ruli of FcR gamma(-/-) mice. The glomeruli of CD40(-/-) mice were almost no rmal. Immunohistochemistry revealed the binding of rabbit IgG to the GBM in all mice injected with anti-GBM antibody. However, depositions of mouse Ig G and complement to the glomeruli were not observed in CD40(-/-) mice, and deposition of fibrin was not observed in FcR gamma(-/-) or CD40(-/-) mice. These findings suggest that Fc gamma R may initiate anti-GBM antibody-media ted renal disease. We conclude that Fc gamma R rather than the complement s ystem is critically involved in the development of type II hypersensitivity diseases.