Follicular dendritic cells (FDC) are found in germinal centers and may play an important role in germinal center (GC) B cell development. However, very little is known about FDC because it is very difficult to obtain a pure preparation of FDC. To aid in the purification of human FDC, we produced a mouse monoclonal antibody named HJ2 that immunohistochemically stains FDC in various lymphoid tissues. Isolated HJ2+ cells obtained by flow cytometric cell sorting exhibit morphological features associated with FDC and display numerous FDC-associated surface markers, but do not express T cell and B cell markers. Taken together, these findings indicate that HJ2 binds FDC and can be used to purify human FDC. Phenotypic studies of purified FDC revealed that FDC express large amounts of the complement (C)-regulatory proteins CD46, CD55, and CD59. By deactivating C, these proteins may safeguard FDC from membranolysis by surface-bound C containing immune complexes. To begin studies of FDC function, we cultured purified FDC and found they survive for at least 2 weeks in vitro. Furthermore, FDC were potent stimulators of allogeneic peripheral blood mononuclear cells and a T cell line in mixed lymphocyte cultures, and on a cell basis, FDC were more active than B cells. The purification of functionally active human FDC should facilitate studying the role of FDC in B cell development within GC. © 1994 Academic Press Inc.