Complement-mediated delay in immune complex clearance from the blood owing to reduced deposition outside the reticuloendothelial system

The effect of serum complement upon the blood clearance rate and tissue distribution of intravenously injected small immune complexes formed between 125-labelled dinitrophenyl (DNP)-conjugated human serum albumin and rabbit IgG-anti-DNP antibodies was studied in mice. Immune complexes formed in the absence of complement (i.e. in phosphate-buffered saline or in the presence of complement-depleted serum from mice treated with cobra venom factor) were cleared from the blood at a higher rate than was the antigen injected alone. In contrast, immune complexes formed in the presence of fresh normal mouse serum were cleared from the blood at the same rate as was the native antigen. Immune complexes formed in the presence of complement were eliminated mainly by the liver. The complexes formed in the absence of complement also became located to the liver to approximately the same extent, but an even larger proportion of these immune complexes was deposited outside the reticuloendothelial system. It is concluded that serum complement may inhibit IgG-mediated clearance of antigen, probably by increasing the solubility of the complexes, thereby reducing the risk of deposition outside the reticuloendothelial system.