Naturally Occurring Circulating Immune Complexes: Normal Human Serum Contains Idiotype-Anti-Idiotype Complexes Dissociable by Certain IgG Antiglobulins

Abstract

Sera from 19 of 23 healthy subjects contained a 24 to 26S complex (NTC). When passed over heat-aggregated IgG (HAGG) Sepharose, the NTC complex dissociated into a 7S IgG that was cytotoxic for malignant melanoma cells, and into an IgG antiglobulin (NTC antiglobulin) that only reacted with autologous cytotoxin. Prior incubation with soluble extracts of melanoma cells, but not with extracts of colon cancer or sarcoma, blocked recombination of isolated cytotoxin with NTC antiglobulin. Thus, NTC antiglobulin had attributes of an anti-idiotype. Cohn Fr II contained NTC complexes from many donors. A second IgG antiglobulin (ACF) was found in sera from patients with advanced cancer or rheumatoid arthritis. When added to normal donor sera, ACF caused NTC antiglobulin and 7S cytotoxin to dissociate. ACF combined with Fab′ of the allogeneic NTC cytotoxin to create a new complex that facilitated complement-dependent cytolysis of malignant melanoma cells. Sera with ACF activity also contained NTC. However, the cytotoxin in these sera was not detectable until the endogenous ACF and NTC antiglobulin had been removed by adsorption to HAGG Sepharose. In ACF-containing sera, ACF fixed to NTC antiglobulin but would not react with the cytotoxin. In contrast, ACF reacted with the cytotoxin but not NTC antiglobulin in allogeneic sera. Thus, some natural antibodies circulate with their antigen-combining sites blocked by endogenous antiglobulins. Other antiglobulins, such as ACF, can facilitate detection of these blocked antibodies if they react with the components of the complex in a way that facilitates their dissociation.