Follicular regulatory T (Tfr) cells have specialized roles in modulating Tfh help to B cells. However, the precise role of Tfr cells in controlling antibody responses to foreign and autoantigens in vivo is still unclear due to a lack of specific tools. We developed a Tfr-deleter mouse that selectively deletes Tfr cells, facilitating temporal studies. We found Tfr cells regulate early, but not late, germinal center (GC) responses to control antigen-specific antibody and B cell memory. Deletion of Tfr cells also resulted in increased self-reactive IgG and IgE. The increased IgE levels led us to interrogate the role of Tfr cells in house dust mite (HDM) models. We found Tfr cells control Tfh13 cell-induced IgE. In vivo, loss of Tfr cells increased HDM-specific IgE and lung inflammation. Thus, Tfr cells control IgG and IgE responses to vaccines, allergens and autoantigens and exert critical immunoregulatory functions prior to GC formation. Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

Over the past 20 years, the development of newer immunosuppressive drugs has improved short-term survival after kidney transplantation. 1 However, long-term survival has not substantially improved. Long-term graft loss has been attributed to chronic antibody-mediated rejection (AbMR) caused by donorspecific antibodies (DSAs). 1,2 DSA can be preexisting or can arise