Direct evidence that human follicular dendritic cells (FDC) rescue germinal centre B cells from death by apoptosis.

It is supposed that FDC have a pivotal role in the rescue of germinal centre (GC) B lymphocytes from apoptosis. However, formal proof for this hypothesis has not as yet been presented. In the present study FDC and GC B cells were isolated from human tonsils and cultured. When brought into culture FDC and B cells rapidly formed spherical clusters. T cells were not observed inside these clusters. At different time points cultures of FDC and B cells were supravitally stained with Hoechst 33258 or acridine orange and examined by direct observation using fluorescence microscopy. Viable B cells appeared to be profoundly restricted to clusters, whereas cells not taking part in clusters all had an apoptotic appearance. The formation of clusters could be prevented by addition of MoAbs against CD11a (LFA-1 alpha) or CD49d (VLA-4 alpha), resulting in an apoptotic appearance of virtually all B lymphocytes. The present data demonstrate that a physical interaction between FDC and germinal centre B lymphocytes is able to rescue the latter from apoptotic cell death.