Naive B cells participate in secondary antibody response via immune complex mediated activation (84.6)

Abstract

Abstract The adaptive immune system confers survival advantage to the host by its inherent ability to respond to a plethora of pathogens and its ability to never forget an antigenic insult. In the case of humoral immune responses, repeat antigenic exposure leads to a secondary antibody response that is 2-3 orders of magnitude greater than the primary. This increased efficacy is due to the production of amplified levels of antigen-specific antibody, as well as the accelerated kinetics of their production. Current dogma holds that this response results from activation of memory B cells, which are formed following primary exposure and can rapidly produce large quantities of specific antibody upon secondary exposure. Our research, however, suggest that memory B cells may not be the chief source of antibody during the secondary response. Using a hapten model system we have shown that the phenomena associated with secondary responses - increased antibody levels and accelerated kinetics of antibody production - can be recapitulated by primary immunization with immune complexes. This suggests that immune complexes are able to activate antigen-inexperienced naive B cells in such a manner that their response mirrors a secondary response. Additionally we have found that blocking the Fc receptor binding activity of immune complexes inhibits the secondary antibody response. We propose that immune complexes are formed upon secondary antigen exposure, and that these complexes enhance the secondary antibody response through naive B cell activation.