Identification of a T follicular helper cell subset that drives anaphylactic IgE.
Cross-linking of high-affinity IgE results in the life-threatening allergic reaction, anaphylaxis. Yet the cellular mechanisms that induce B cells to produce IgE to allergens remain poorly understood. T follicular helper (Tfh) cells direct the affinity and isotype of antibodies produced by B cells. Although Tfh cell-derived IL-4 is necessary for IgE production, it is not sufficient. We report a rare population of IL-13-producing Tfh cells present in mice and humans with IgE to allergens, but not when allergen-specific IgE was absent or only low-affinity. These "Tfh13" cells have an unusual cytokine profile (IL-13hiIL-4hiIL-5hiIL-21lo) and co-express BCL6 and GATA3. They were required for production of high- but not low-affinity IgE and subsequent allergen-induced anaphylaxis. Blocking Tfh13 cells may represent an alternative therapeutic target to ameliorate anaphylaxis.