The generation of autoantibody and subsequent tissue deposition of imm
une complexes (IC) is thought to trigger the pathogenic consequences o
f systemic autoimmune disease. Modulation of the autoantibody response
disrupts pathogenesis by preventing the formation of ICs; however, un
coupling IC formation from subsequent inflammatory responses seems unl
ikely because of the apparent complexity of the IC-triggered inflammat
ory cascade. However, the disruption of a single gene, which encodes t
he gamma chain of the Fc receptor, was found to achieve this uncouplin
g in a spontaneous model of lupus nephritis, the New Zealand Black/New
Zealand White (NZB/NZW) mouse. Gamma chain-deficient NZB/NZW mice gen
erated and deposited IC and activated complement, but were protected f
rom severe nephritis, thus defining another potential pathway for ther
apeutic intervention in autoimmune disease.