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Expansion of follicular helper T cells in the absence of Treg cells: Implications for loss of B‐cell anergy

The maintenance of B‐cell anergy is essential to prevent the production of autoantibodies and autoimmunity. However, B‐cell extrinsic mechanisms that regulate B‐cell anergy remain poorly understood. We previously demonstrated that regulatory T (Treg) cells are necessary for the maintenance of B‐cell anergy. We now show that in Treg‐cell‐deficient mice, helper T cells are necessary and sufficient for loss of B‐cell tolerance/anergy. In addition, we show that the absence of Treg cells is associated with an increase in the proportion of CD4+ cells that express GL7 and correlated with an increase in germinal center follicular helper T (GC‐TFH) cells. These GC‐TFH cells, but not those from Treg‐cell‐sufficient hosts, were sufficient to drive antibody production by anergic B cells. We propose that a function of Treg cells is to prevent the expansion of TFH cells, especially GC‐TFH cells, which support autoantibody production.