EXPRESSION OF COMPLEMENT RECEPTOR-1 AND RECEPTOR-2 ON FOLLICULAR DENDRITIC CELLS IS NECESSARY FOR THE GENERATION OF A STRONG ANTIGEN-SPECIFIC IGG RESPONSE

Two mechanisms could account for the impaired humoral immune response found in Cr2(-/-) mice. The absence of complement receptors 1 and 2 (C R1, CR2) on B cells could affect their activation Alternatively, impai red Ag trapping by follicular dendritic cells (FDC) could affect B cel l maturation into Ig-secreting or memory B cells, To compare the roles of CR1 and CR2 on B cells vs FDC in this abnormal response, bone marr ow (BM) chimeric mice were generated and immunized with specific T-dep endent Ags, The primary and secondary Ab response was measured. Cr2(+/ +) animals reconstituted with a Cr2(-/-) BM generated a diminished but detectable humoral immune response compared with controls. When injec ted with preformed immune complexes (IC), these mice maintained follic ular IC localization. Cr2(-/-) animals reconstituted with a Cr2(+/+) B M had an initial rise in the Ab titer, but were unable to maintain it as shown by a pronounced decrease in the Ige titer, This defect persis ted during the secondary immune response. Follicular IC trapping was a lso impaired. Despite the abnormal Ab response, germinal center format ion was retained in all of the chimeric animals. These experiments are the first to demonstrate an absolute requirement for CR1 and CR2 expr ession on FDC in the generation of a normal humoral immune response.