IL-21 is a broad negative regulator of IgE class switch recombination in mouse and human B cells.

The Journal of Experimental Medicine
Zhiyong YangChristopher D C Allen

Abstract

IgE antibodies may elicit potent allergic reactions, and their production is tightly controlled. The tendency to generate IgE has been thought to reflect the balance between type 1 and type 2 cytokines, with the latter promoting IgE. Here, we reevaluated this paradigm by a direct cellular analysis, demonstrating that IgE production was not limited to type 2 immune responses yet was generally constrained in vivo. IL-21 was a critical negative regulator of IgE responses, whereas IFN-γ, IL-6, and IL-10 were dispensable. Follicular helper T cells were the primary source of IL-21 that inhibited IgE responses by directly engaging the IL-21 receptor on B cells and triggering STAT3-dependent signaling. We reconciled previous discordant results between mouse and human B cells and revealed that the inhibition of IgE class switch recombination by IL-21 was attenuated by CD40 signaling, whereas IgG1 class switch recombination was potentiated by IL-21 in the context of limited IL-4. These findings establish key features of the extrinsic regulation of IgE production by cytokines.

References

Jan 11, 1990·Annual Review of Immunology·F D FinkelmanW E Paul
Oct 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·A StrasserA W Harris
Dec 31, 1997·American Journal of Respiratory Cell and Molecular Biology·G G BruselleR A Pauwels
May 17, 2000·Proceedings of the National Academy of Sciences of the United States of America·M J MäkeläE W Gelfand
Jun 10, 2000·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·K G TournoyR A Pauwels
Feb 15, 2002·The European Respiratory Journal·H Renz, U Herz
Nov 26, 2002·Science·Katsutoshi OzakiWarren J Leonard
Apr 12, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Devangi S MehtaMichael J Grusby
Sep 2, 2003·Nature Reviews. Immunology·Raif S GehaScott R Brodeur
Feb 6, 2004·The Journal of Allergy and Clinical Immunology·Sergio Romagnani
Jun 24, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Haoli JinThomas R Malek
Oct 20, 2004·The Journal of Experimental Medicine·Axel KalliesStephen L Nutt
May 28, 2005·Cellular Immunology·Nancy WoodMarion T Kasaian
Oct 15, 2005·Blood·Jamie L FornekGeoffrey S Kansas
May 23, 2006·Nature Immunology·Robert L Coffman
Sep 1, 2006·Journal of Leukocyte Biology·Haoli Jin, Thomas R Malek
Oct 4, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jérôme PèneHans Yssel
Oct 4, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kim L GoodStuart G Tangye
Dec 21, 2006·The Journal of Experimental Medicine·Michishige HaradaMasaru Taniguchi
Feb 13, 2007·Immunity·Agustin ErazoJuan J Lafaille
May 17, 2007·International Archives of Allergy and Immunology·Atsuki FukushimaHisayuki Ueno
Jun 27, 2008·Blood·Danielle T AveryStuart G Tangye
Oct 18, 2008·European Journal of Immunology·Gertrude Achatz-StraussbergerGernot Achatz
Jan 10, 2009·Annual Review of Immunology·Thomas KornVijay K Kuchroo
Jan 14, 2009·The Journal of Experimental Medicine·Oliver DienzMercedes Rincon
Jul 14, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Wendy A NeveuMercedes Rincon
May 10, 2011·Nature Immunology·Brandon M SullivanRichard M Locksley
Dec 6, 2011·Nature Immunology·Hong-Erh LiangRichard M Locksley
Oct 3, 2012·The Journal of Experimental Medicine·Tomohiro KajiToshitada Takemori
Aug 28, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kristin HollisterAlexander L Dent
Nov 13, 2013·The Journal of Experimental Medicine·Jin-Shu HeMaria A Curotto de Lafaille
Mar 4, 2014·The Journal of Allergy and Clinical Immunology·Mübeccel Akdis, Cezmi A Akdis

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Citations

Dec 12, 2020·European Journal of Immunology·Paul Haase, David Voehringer
Dec 19, 2020·The Journal of Allergy and Clinical Immunology·Kelly BrutonManel Jordana
Mar 2, 2021·The Journal of Clinical Investigation·Garrett J PatrickLloyd S Miller
Dec 9, 2020·Allergology International : Official Journal of the Japanese Society of Allergology·Kei Haniuda, Daisuke Kitamura
Apr 24, 2021·Journal of Autoimmunity·Tina De Bruyn CarlierInge Kortekaas Krohn
Jun 18, 2021·ImmunoTargets and Therapy·Joshua F E KoenigManel Jordana
Jun 18, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·David PossamaïRéjean Lapointe
Jul 4, 2021·Current Opinion in Immunology·Adam K Wade-Vallance, Christopher D C Allen

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Methods Mentioned

BETA
flow cytometry
FACS
flow cytometric sorting
PCR

Software Mentioned

PhosFlow
GraphPad Prism
FlowJo
GraphPad Statistics Guide

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