Role of complement receptor type 2 and endogenous complement in the humoral immune response to conjugates of complement C3d and pneumococcal serotype 14 capsular polysaccharide.

Conjugation of the complement fragment C3d to both T-cell-dependent (TD) protein and T-cell-independent type 2 (TI-2) polysaccharide antigens enhances the humoral immune response in mice immunized with either type of antigen. However, the ability of C3d-protein conjugates to enhance the antibody response in mice deficient in complement receptor types 1 and 2 (CR1 and CR2) has raised questions about the role of C3d-CR2 interactions in the adjuvant effect of C3d. In this study, we examined the role of CR2 binding and endogenous complement activation in the antibody response to conjugates of C3d and serotype 14 pneumococcal capsular polysaccharide (PPS14). To block binding of PPS14-C3d conjugates to CR2, mice were immunized with a mixture of vaccine and (CR2)2-immunoglobulin G1 (IgG1). Mice receiving (CR2)2-IgG1 at the time of primary immunization had a marked reduction in the primary anti-PPS14 antibody response but an enhanced secondary anti-PPS14 response, suggesting that C3d-CR2 interactions are required for the primary response but can have negative effects on the memory response. Further, compared with mice receiving PPS14-C3d having a high C3d/PPS14 ratio, mice immunized with PPS14-C3d with low C3d/PPS14 ratios had an enhanced secondary antibody response. Treatment of mice with cobra venom factor to deplete complement had insignificant effects on the antibody response to PPS14-C3d. Experiments with CBA/N xid mice confirmed that PPS14-C3d conjugates retain the characteristics of TI-2 rather than TD antigens. Thus, the adjuvant effect of C3d conjugated to PPS14 requires C3d-CR2 interactions, does not require activation of endogenous complement, and is not mediated by TD carrier effects.

[A congenital deficiency of the C3 fraction of complement. A familial study]. / Deficit congenital de la fraction C3 du complement: Etude familiale.

The innate deficit of the third constituent of the complement is extremely rare, it appears clinically as a deficit of the humorale immunity. We report a case of C3 deficit in a 6 year old Tunisian child, who presents a psychomotor delay and recurrent infections. The investigation of the complement system profile by an immunochemical test of the children's serum shows an absence of C3 and C3d, associated to a loss of classic and alternate hemolytic pathway activities. The addition of functional C3 in the deficient serum restores the global hemolytic activity. The reconstruction of the hemolytic activity is dose dependent of C3 added quantity. The rate of C3 is lowered in the parent's with a 50% decrease of the global hemolytic activity. Immunochemical measurement of C3d confirms the absence of any C3 catabolism product in vivo. On the other hand (factor I) show a normal rate to all the family members.