A follicular regulatory Innate Lymphoid Cell population impairs interactions between germinal center Tfh and B cells

Innate Lymphoid Cells (ILCs) are immune cells typically found on mucosal surfaces and in secondary lymphoid organs where they regulate the immune response to pathogens. Despite their key role in the immune response, there are still fundamental gaps in our understanding of ILCs. Here we report a human ILC population present in the follicles of tonsils and lymph nodes termed follicular regulatory ILCs (ILC_FR) that to our knowledge has not been previously identified. ILC_FR have a distinct phenotype and transcriptional program when compared to other defined ILCs. Surprisingly, ILC_FR inhibit the ability of follicular helper T (Tfh) cells to provide B cell help. The localization of ILC_FR to the germinal centers suggests these cells may interfere with germinal center B cell (GC-B) and germinal center Tfh cell (GC-Tfh) interactions through the production of transforming growth factor beta (TGF-β. Intriguingly, under conditions of impaired GC-Tfh-GC-B cell interactions, such as human immunodeficiency virus (HIV) infection, the frequency of these cells is increased. Overall, we predict a role for ILC_FR in regulating GC-Tfh-GC-B cell interactions and propose they expand in chronic inflammatory conditions.