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

Authors

Uthaman Gowthaman
Jennifer S Chen
Biyan Zhang
William F Flynn, The Jackson LaboratoryFollow
Yisi Lu
Wenzhi Song
Julie Joseph
Jake A Gertie
Lan Xu
Magalie A Collet, The Jackson LaboratoryFollow
Jessica D S Grassmann, The Jackson LaboratoryFollow
Tregony Simoneau
David Chiang
M Cecilia Berin
Joseph E Craft
Jason S Weinstein
Adam Williams, The Jackson LaboratoryFollow
Stephanie C Eisenbarth

Document Type

Article

Publication Date

8-30-2019

Keywords

JGM

JAX Source

Science 2019 Aug 30; 365(6456):883

Volume

365

Issue

6456

ISSN

1095-9203

PMID

31371561

DOI

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

Grant

AI135221,AI133440

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_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_FH13" cells have an unusual cytokine profile (IL-13^hiIL-4^hiIL-5^hiIL-21^lo) and coexpress the transcription factors BCL6 and GATA3. T_FH13 cells are required for production of high- but not low-affinity IgE and subsequent allergen-induced anaphylaxis. Blocking T_FH13 cells may represent an alternative therapeutic target to ameliorate anaphylaxis.

Recommended Citation

Gowthaman U, Chen J, Zhang B, Flynn W, Lu Y, Song W, Joseph J, Gertie J, Xu L, Collet M, Grassmann J, Simoneau T, Chiang D, Berin M, Craft J, Weinstein J, Williams A, Eisenbarth S. Identification of a T follicular helper cell subset that drives anaphylactic IgE. Science 2019 Aug 30; 365(6456):883