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Science. 2019 Aug 1. pii: eaaw6433. doi: 10.1126/science.aaw6433. [Epub ahead of print]

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

Author information

1
Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
2
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
3
The Jackson Laboratory for Genomic Medicine, Farmington, CT 06030, USA.
4
The Asthma Center, CT Children's Medical Center, Hartford, CT 06106, USA.
5
Jaffe Food Allergy Institute and Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
6
Center for Immunity and Inflammation, Rutgers New Jersey Medical School, Newark, NJ 07101, USA.
7
The Jackson Laboratory for Genomic Medicine, Farmington, CT 06030, USA. stephanie.eisenbarth@yale.edu adam.williams@jax.org.
8
The Department of Genetics and Genome Sciences, University of Connecticut Health Center, Farmington, CT 06032, USA.
9
Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520, USA. stephanie.eisenbarth@yale.edu adam.williams@jax.org.

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.

PMID:
31371561
DOI:
10.1126/science.aaw6433

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