The role of complement in the induction of antibody responses.

To determine the effect of complement on the normal antibody response to T cell-dependent antigens, we immunized normal and C4 deficient guinea-pigs with bacteriophage phi X 174. Following primary immunization with a standard dose (2 X 10(9) PFU/Kg) given intravenously. C4 deficient guinea-pigs produced less antibody than normal guinea-pigs and were unable to maintain measurable antibody levels. Following secondary immunization, antigen clearance of C4 deficient guinea-pigs was delayed and the subsequent antibody response was identical to their primary response without amplification or isotype switch. Increased antigen dose and administration of antigen in adjuvants into footpads improved the responses but did not make them normal. The primary and secondary responses became essentially normal, however, when small amounts of normal guinea-pig serum were given to the deficient animals at the time of the primary (but not the secondary) immunization. We postulate that the contribution of complement to the mature humoral immune response is related to activation of C3. Our data show that antigen initiates a primary immune response. The resultant antigen-antibody complexes interact with complement and are then non-specifically trapped by C3 receptors on dendritic cells, B cells and macrophages. Thus, antigen is selectively accumulated within the lymphoid organs and in turn 'captures' antigen specific B cells by interaction of the trapped antigen with antigen specific sIg. The approximation of specific lymphoid cells, macrophages and antigen permits generation of specific memory cells and ensures prompt, mature antibody response on subsequent antigen exposure.