RESISTANCE OF FC RECEPTOR-DEFICIENT MICE TO FATAL GLOMERULONEPHRITIS

Immune complex-mediated inflammation is a common mechanism of various autoimmune diseases. Glomerulonephritis (GN) is one of these diseases, and the main mechanism of the induction of GN has been unclear. We ex amined the contribution of Fc receptors in the induction of nephrotoxi c GN by establishing and analyzing mice deficient in the Fc receptor g amma chain (FcR gamma). Whereas all wild-type mice died from severe gl omerulonephritis with hypernitremia by administration of anti-glomerul ar basement membrane (GBM) antibodies, all FcR gamma-deficient mice su rvived. Histologically, wild-type mice showed glomerular hypercellular ity and thrombotic changes, whereas the renal tissue in FcR gamma-defi cient mice was almost intact. Deposition of anti-GBM antibody as well as complement components in the GEM were equally observed in both wild -type and knockout mice. These results demonstrate that the triggering of this type of glomerulonephritis is completely dependent on FcR(+) cells.