FOLLICULAR DENDRITIC CELL-DERIVED ANTIGEN AND ACCESSORY ACTIVITY IN INITIATION OF MEMORY IGG RESPONSES IN-VITRO

Follicular dendritic cells (FDC) release Ag in developing germinal cen ters in the form of immune complex-coated bodies (iccosomes). Iccosome s are endocytosed by B cells, and the B cells process and present the FDC-derived Ag to T cells. By 3 days after Ag challenge, Ab-forming ce lls producing IgG specific for the iccosomal Ag emerge from the develo ping germinal centers and home to the bone marrow, where most Ab in a secondary response are produced, In addition to providing Ag, FDC exhi bit potent accessory activities that promote B cell proliferation, The se observations prompted the hypothesis that both FDC-derived Ag and F DC-derived Ag-independent secondary signal(s) are essential for optima l secondary Ab responses, To test this hypothesis, methods were develo ped to separate Ag-bearing iccosomes from intact FDC, and we then exam ined the ability of isolated iccosomes to elicit secondary Ab response s in vitro in the presence and absence of intact FDC, In the absence o f FDC, iccosomes bearing the appropriate Ag elicited only minimal leve ls of specific IgG, Proliferation studies revealed that iccosomes lack ed the FDC accessory activity necessary to augment B cell proliferatio n. When a source of FDC lacking the relevant Ag but exhibiting accesso ry activity was added to the iccosomal/Ag/lymphocyte mixture, dramatic increases in IgG specific for the iccosomal Ag were obtained (increas es were from low ng/ml to mu g/ml levels of specific IgG), The results suggest the concept that Ag on FDC or on iccosomes signals B cells th rough B cell Ag receptor, the iccosome provides these B cells with Ag necessary to process and elicit T cell help, and a secondary signal(s) necessary to optimize the memory response is delivered to B cells by FDC in an Ag-nonspecific fashion.