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

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.