Interleukin-10 from CD4+ follicular regulatory T cells promotes the germinal center response

CD4(+) follicular regulatory T(T-fr) cells suppress B cell responses through modulation of follicular helper T (T-fh) cells and germinal center (GC) development. We found that T-fr cells can also promote the GC response through provision of interleukin-10 (IL-10) after acute infection with lymphocytic choriomeningitis virus (LCMV). Sensing of IL-10 by B cells was necessary for optimal development of the GC response. GC B cells formed in the absence of T-reg cell-derived IL-10 displayed an altered dark zone state and decreased expression of the transcription factor Forkhead box protein 1(FOXO1). IL-10 promoted nuclear translocation of FOXO1 in activated B cells. These data indicate that T-fr cells play a multifaceted role in the fine-tuning of the GC response and identify IL-10 as an important mediator by which T-fr cells support the GC reaction.