EVIDENCE FOR AN IMPORTANT INTERACTION BETWEEN A COMPLEMENT-DERIVED CD21 LIGAND ON FOLLICULAR DENDRITIC CELLS AND CD21 ON B-CELLS IN THE INITIATION OF IGG RESPONSES

The addition of Ags to mononuclear leukocyte cultures typically elicit s modest Ab responses, implying that cosignals beyond those provided b y T cells and macrophages may be needed. Recently, we reported that Ab responses could be dramatically enhanced (10-1000-fold) by the additi on of follicular dendritic cells (FDC), suggesting that FDC may provid e an important costimulatory signal. This result prompted a study of m olecules involved in FDC-mediated enhancement of Ab responses stimulat ed by specific Ag with memory T and B cells or nonspecifically by the addition of LPS, In this study, we report evidence supporting the conc ept that FDC bear a ligand that engages complement receptor II (CR2 or CD21) on B cells and provides a critical cosignal for both Ag-specifi c and polyclonal responses. A blockade of the CR2 ligand on FDC by the use of soluble CR2 or a blockade of CR2 on B cells by use of CR2 knoc kout mice (or B cells with CR2 blocked) reduced Ab responses from the mu g/ml to the ng/ml range (10-1000-fold reductions). FDC from C3 knoc kout mice, which cannot generate the CR2-binding fragments (iC3b, C3d, and C3dg), were unable to provide costimulatory activity, suggesting the CR2 ligand on FDC consists of C3 fragments, FDC trap complement-ac tivating Ag-Ab complexes, and it appears that FDC present B cells with both specific Ag to engage B cell receptors and a CR2 ligand to engag e B cell-CR2, In short, optimal induction of specific Ab responses app ears to require the combination of specific Ag and costimulatory molec ules from both T cells and FDC.