Identification of a T follicular helper cell subset that drives anaphylactic IgE

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