Mode of Action of Adjuvants: Effects on Antibody Responses to Macrophage-Associated Bovine Serum Albumin

Abstract Primary and secondary antibody responses were measured in CBA mice after injecting them with different primary doses of free bovine serum albumin (free BSA) or BSA taken up by syngeneic macrophages (MBSA). The antibody responses to MBSA were much higher than those to FBSA, and the slopes of the dose-response curves differed significantly. When FBSA was administered shortly before MBSA, the antibody responses were less than when MBSA was given alone. It is suggested that FBSA elicits two competitive responses in immunocompetent cells: immunization and the induction of tolerance; with MBSA the balance is changed strongly toward immunization. Potent adjuvants, injected prior to FBSA, heightened antibody responses to approximately the level produced by the same doses of MBSA. This suggested that adjuvants can also prevent the tolerance-inducing effect of FBSA. MBSA is retained by macrophages incubated in vitro for several hours, and the immunogenicity of the retained BSA does not decrease. MBSA gives rise to an antibody response in irradiated recipients only if they have been reconstituted with syngeneic lymphocytes. MBSA in E. coli lipopolysaccharide (LPS)-treated macrophages induced consistently higher antibody responses in normal mice than MBSA bound by untreated macrophages. LPS treatment of lymphocytes used to reconstitute irradiated animals had no detectable effect on antibody responses. This suggests that the effects of adjuvants may be exerted at least partly on macrophages. LPS had no demonstrable effect on the uptake or degradation of antigen by macrophages.