Roles of anti-C1q antibodies in the development of glomerular injury and antinuclear antibodies. (A) Anti-C1q antibodies (in yellow) such as JL-1 recognize the collagen-like “tails” of C1q in much the same manner as they would recognize any antigen through the F(ab) antigen-recognition domain. The administration of C1q and anti-C1q is not sufficient to cause glomerular injury as shown by Trouw et al. (6). However, when C1q-fixing anti-glomerular basement membrane (GBM) antibodies (in green) are first administered to mice, then C1q is able to bind to the Fc domain as it normally does. This brings anti-C1q antibodies into the glomerulus, resulting in sufficient complement activation to result in the generation of C3a, C5a, and MAC and the development of glomerulonephritis (B). As an alternate means by which anti-C1q antibodies could promote lupus-like autoimmunity, these antibodies could interfere with the normal ability of C1q to recognize apoptotic bodies containing DNA and other nuclear autoantigens (C). In this scenario, impaired clearance of apoptotic bodies, or clearance in a proinflammatory setting due to complement activation caused by the anti-C1q antibodies, could promote the development of autoantibodies that target DNA and other nuclear antigens, which is similar to what occurs when C1q is absent due to a genetic deficiency.