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

초록

Evidence for the immunoregulatory function of lipid molecules in addition to proteins is accumulating. Based on our previous reports on the production of prostaglandin E-2 (PGE(2)) 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 PGE(2) 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 PGE(2), which was significantly inhibited in the presence of indomethacin. The viable recovery was due to the prevention of cell death by PGE(2) and beraprost but did not result from augmented proliferation of GC B cells. The effect of PGE(2) 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 PGE(2). Finally, PGE(2) 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. (C) 2013 Elsevier Ltd. All rights reserved.

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