Follicular regulatory T cells control humoral and allergic immunity by restraining early B cell responses

Follicular regulatory T (T_FR) cells have specialized roles in modulating follicular helper T (T_FH) cell activation of B cells. However, the precise role of T_FR cells in controlling antibody responses to foreign antigens and autoantigens in vivo is still unclear due to a lack of specific tools. A T_FR cell-deleter mouse was developed that selectively deletes T_FR cells, facilitating temporal studies. T_FR cells were found to regulate early, but not late, germinal center (GC) responses to control antigen-specific antibody and B cell memory. Deletion of T_FR cells also resulted in increased self-reactive immunoglobulin (Ig) G and IgE. The increased IgE levels led us to interrogate the role of T_FR cells in house dust mite models. T_FR cells were found to control T_FH13 cell-induced IgE. In vivo, loss of T_FR cells increased house-dust-mite-specific IgE and lung inflammation. Thus, T_FR cells control IgG and IgE responses to vaccines, allergens and autoantigens, and exert critical immunoregulatory functions before GC formation.