C3- and T-cell-dependent adjuvant activity of in vivo formed immune complexes.

The effects of polyclonal antibodies to mouse serum components on the primary humoral immune response of mice in vivo were studied. It was observed that rabbit IgG to complement component C3 and albumin and mouse IgG to C5, but also heat-aggregated non-immune rabbit IgG, enhanced the agglutinating antibody response to sheep erythrocytes (SRBC). Since the increase in response was only observed when antigen and antibodies were administered via the same route (i.p.), immunological adjuvant activity was implicated. Ineffectiveness of anti-C5 IgG in C5-deficient mice indicated that the antibody-induced adjuvant activity is mediated by in vivo formed immune complexes (IC). The adjuvant activity of IC was reduced by selective C3-depletion of animals, pointing to a requirement of C3. The effect of variations in other parameters was studied with anti-C3 and anti-C5 IgG as immunoadjuvant. The immunostimulatory effect was most pronounced when the antibodies were administered simultaneously with or shortly before antigen. Treatment of animals with antibodies one or two days before antigen, however, resulted in a suppression of the response. The response to thymus-independent antigens was not enhanced by anti-C3 nor by anti-C5 IgG. Optimal adjuvant activity of anti-C3 IgG was observed at low antigen doses. Nude mice were insensitive to the immunopotentiating effect of anti-C3 and so was the F1 progeny of BALB/c male and CBA/N female mice expressing a B-cell maturation defect. C5 deficiency and lipopolysaccharide (LPS) non-responsiveness did not affect the adjuvant activity of in vivo formed C3-anti-C3 IC.