RABBIT COMPLEMENT LYSES TUMOR-CELLS WITHOUT MASSIVE C3 DEPOSITION

These experiments were performed to determine why rabbit complement ly ses tumor cells very efficiently, while not having particularly strong activity in hemolytic assays or in any other complement assay. The ta rget cells used were human tumor cells coated with three different mou se IgG(2a) monoclonal antibodies, and complement from 5 mammalian spec ies were tested. In antibody titration experiments, rabbit complement was found to lyse target cells at a relatively low antibody concentrat ion, insufficient to allow lysis by complement of other species. Since this result was still observed after absorption of rabbit serum with target cells, the potency of rabbit complement cannot be attributed to the presence of natural antibodies. We then assayed C3 deposition on target cells, using two types of I-125-labeled anti-C3 Abs to measure C3 deposition: goat antibodies specific for C3 of the human, guinea pi g, rabbit, rat or mouse, and chicken antibodies to human C3 which cros s-react with C3 of other mammals. Unexpectedly, complement of the huma n, rat, guinea pig, and BUB mouse deposited large amounts of C3 on the surface of target cells, while rabbit complement deposited 100-1,000 fold less. We discuss the possible reasons that C3 deposition does not correlate with cytotoxicity, and may indeed be inversely related. The se data indicate that there is a fundamental difference in the complem ent cascade between rabbits and the other species tested. The potent l ytic activity of rabbit complement is likely to be related to this dif ference, although the mechanism is not yet understood.