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.