The generation of memory cells. I. The role of C3 in the generation of B memory cells.

Adult thymectomized, repopulated mice were chronically depleted of circulating C3 by treatment with cobra venom factor after primary immunization with dinitrophenylated haemocyanin (DNP-KLH). This treatment totally abrogated the development of B-cell memory in such mice, as assayed by a co-operative lymphocyte transfer. The failure of memory development appeared to involve impaired precursor proliferation following priming. It was further shown that the localization of DNP-KLH in splenic lymphoid follicles is both antibody and C3-dependent; thymus-deprived mice make sufficient antibody to DNP-KLH to effect follicular localization of the antigen. On the basis of these and earlier observations we suggest that the development of B-memory cells involves the formation of antigen-antibody-C3 complexes on dendritic cells in lymphoid follicles. C3 may serve to stabilize the antigen bridge between dendritic cells and virgin precursors. In complete contrast, C3 depletion had little effect on the functional expression of primed B cells, thus suggesting that only the early stages of B-cell triggering are C3 dependent.