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

Gowthaman, Uthaman; Chen, Jennifer S; Zhang, Biyan; Flynn, William F; Lu, Yisi; Song, Wenzhi; Joseph, Julie; Gertie, Jake A et al. · Science · 2019

basic_science · Level V

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Abstract

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<sub>FH</sub>) cells direct the affinity and isotype of antibodies produced by B cells. Although T<sub>FH</sub> 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<sub>FH</sub> cells present in mice and humans with IgE to allergens, but not when allergen-specific IgE was absent or only low-affinity. These "T<sub>FH</sub>13" cells have an unusual cytokine profile (IL-13<sup>hi</sup>IL-4<sup>hi</sup>IL-5<sup>hi</sup>IL-21<sup>lo</sup>) and coexpress the transcription factors BCL6 and GATA3. T<sub>FH</sub>13 cells are required for production of high- but not low-affinity IgE and subsequent allergen-induced anaphylaxis. Blocking T<sub>FH</sub>13 cells may represent an alternative therapeutic target to ameliorate anaphylaxis.

Medical subject headings