Title

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

Document Type

Article

Publication Date

8-1-2019

Keywords

JGM

JAX Source

Science 2019 Aug 1 [Epub ahead of print]

PMID

31371561

DOI

https://doi.org/10.1126/science.aaw6433

Grant

AI135221,AI133440

Abstract

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.

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