Cutting edge: C1q protects against the development of glomerulonephritis independently of C3 activation

C1q-deficient (C1qa(-/-)) mice develop antinuclear Abs and glomerulonephrit is (GN) characterized by multiple apoptotic bodies. To explore the contribu tion of C3 activation to the induction of spontaneous GN, C1qa(-/-) mice we re crossed with factor B- and C2-deficient (H2-Bf/C2(-/-)) mice. GN was pre sent in 64% of the 45 C1qa/H2-Bf/C2(-/-) mice compared with 8% of the 65 H2 -Bf/ C2(-/-) mice and none of the 24 wild-type controls. IgG was detected i n the glomeruli of diseased C1qa/H2-Bf/C2(-/-) kidneys. However, glomerular staining for C3 was absent, Increased numbers of glomerular apoptotic bodi es were detected in undiseased C1qa/H2-Bf/C2(-/-) kidneys. These findings s upport the hypothesis that Clq may play a role in the clearance of apoptoti c cells without the necessity for C3 activation and demonstrate that the ac tivation of C3 is not essential for the development of GN in this spontaneo us model of lupus-like disease.