To study the functional role of follicular dendritic cells (FDC) in germinal center (GC)-B cell differentiation, we have established an in vitro experimental model that mimics GC-reactions in vivo. Using this culture system, we have characterized the distinct function of FDC from activated T cells. The primary function of FDC is to prevent apoptosis and support proliferation of GC-B cells, whereas activated T cells induce the differentiation of GC-B cells by providing CD40L and cytokines. Furthermore, we have identified two FDC-signaling molecules that mediate proliferation of GC-B cells in vitro and in vivo.