Activation and proliferation of follicular dendritic cell-like cells by activated T lymphocytes

Follicular dendritic cell (FDC)-like cell lines (HK cells) from human tonsils were established to investigate the functional role of FDC in the germinal centers of lymphoid follicles. Although HK cells exhibited CD21, CD23, DRC-1, CD40, VCAM-1, ICAM-1, and HJ2 that were expressed on human tonsilar FDC at early stages of establishment, they lost DRC-1, CD21, and CD23 within 3 days of culture. Morphologic and functional characterization studies suggest that HK cells are quite distinct from fibroblasts. The growth requirement of HK cells is different from the previously reported FDC-like cell lines. Functionally, these cells bound B cells but not T cells, and supported B cell proliferation. The culture supernatants of HK cells had costimulatory activity on the proliferation of anti-mu- or anti-CD40-activated B cells, and the activity dramatically increased after 12-O-tetradecanoylphorbol 13-acetate stimulation. Interestingly, anti-CD3 Ab activated T cell bound to HK cells, inducing the phenotypic changes and the growth of HK cells. The T-HK cell interactions not only involve the well known adhesion ligand/receptor pathways (VLA-4/VCAM-1 and LFA-1/ICAM-1), but also involve CD40-CD40 ligand as shown by inhibitory effect of soluble CD40 (CD40.Fc). The cellular interactions between T and HK cells and cytokine production suggest that activated T cells not only stimulate resting B cells directly, but also support B cell maturation indirectly by stimulating the development of FDC. Hence HK cells may be useful in identifying the surface molecules and cytokines of FDC involved in the GC formation.