The effects on antibody responses might result from complement activation rather than interference with direct participation of complement in induction. For example C3 fragments can suppress in vitro antigen-induced lymphocyte transformation. However, the inhibition by isolated anti-C3 antibodies of thymus-dependent antibody responses which has been observed in vitro cannot be attributed to the generation of C3 fragments. It seems more likely that the various C3-reactive agents act by reducing functional complement at the site of induction of antibody procluction.
C5- and C6-deficient animals mount normal antibody responses, which, in conjunction with the observed effects of anti-C3 antibodies, indicates that C3 is the important component. C4-deficient guinea pigs, although they can still fix C3 by the alternate pathway, have impaired responses to certain antigens.
The present in vivo results, and other in vitro data, suggest that C3 plays a part in induction of thymus-dependent antibody production, and may, therefore, participate in lymphocyte cooperation. Thymus-dependent presentation of antigen to B cells at the surface of macrophages has been suggested in several hypotheses and there is evidence that B cells undergoing activation to transform and secrete antibody, both in vivo and in vitro, tend to be aligned on the surface of, or clustered around macrophages. In in vitro studies with separated cell populations Feldmann has shown that activated T cells are stimulated by antigen to secrete a specific antigen-binding product. It is apparently a form of IgM which, in complexes with antigen, adheres to the surface of macrophages and leads to triggering of specific B cells to antibody formation.
It is postulated here that C3 may have a role in presentation of antigen to B cells, by enhancing approximation of the different cell types involved in cooperation. Complexes of antigen, either with the putative specific T-cell product or with other immunoglobulin, could fix C3 and then bind to the surface of macrophages which bear a membrane receptor for fixed C3. B cells would, by virtue of their C3 receptor, tend to adhere nonspecifically to macrophages bearing C3-coated complexes, and if a B cell had the appropriate specific antigen receptors it might then recognize the presented antigen and be triggered. It is relevant that while both IgG and IgM-antigen-C3 complexes bind to macrophages, only the IgM complexes are held on the cell surface and are not phagocytosed. Also passively administered IgM antibody, as opposed to IgG antibody, can enhance active antibody production in vivo to the specific antigen.
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