Human follicular dendritic cells promote germinal center B cell survival by providing prostaglandins

Abstract

Evidence for the immunoregulatory function of lipid molecules in addition to proteins is accumulating. Based on our previous reports on the production of prostaglandin E2 (PGE2) and prostacyclin by human follicular dendritic cells (FDCs), we hypothesized that these prostaglandins (PGs) have a regulatory effect on the survival, proliferation, and differentiation of germinal center B (GC) cells. We observed that PGE2 and a prostacyclin analog (beraprost) specifically enhanced the viable recovery of GC B cells in dose-dependent manners. FDC-like cells also mimicked the effect of PGE2, which was significantly inhibited in the presence of indomethacin. The viable recovery was due to the prevention of cell death by PGE2 and beraprost but did not result from augmented proliferation of GC B cells. The effect of PGE2 and beraprost was manifest when they were added at early times of the culture. Interestingly, we found that the combined addition of a pan-caspase inhibitor and a necroptosis inhibitor gave rise to a similar result to PGE2. Finally, PGE2 and beraprost enhanced the generation of both CD20−CD38+ plasma cells and CD20+CD38− memory B cells from GC B cells. Our current data suggest that FDCs play an important function of sustaining GC B cell survival by providing PGs. Our data also implies that selective cyclooxygenase inhibitors administered during infection or vaccination may have an adverse effect on the course of humoral immune response.