{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:39:27Z","timestamp":1791236367193,"version":"4.1.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2017,7,1]],"date-time":"2017-07-01T00:00:00Z","timestamp":1498867200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>IgE production plays a crucial role in protective as well as pathogenic type 2 immune responses. Although the cytokine IL-4 is required for the development of IgE-producing plasma cells, the source of IL-4 and cellular requirements for optimal IgE responses remain unclear. Recent evidence suggests that T follicular helper (Tfh) cells are the primary producer of IL-4 in the reactive lymph node during type 2 immune responses. As Tfh cells are also required for the development of plasmablasts derived from germinal center and extrafollicular sources, we hypothesized that this cell subset is essential for the IgE plasmablast response. In this study, we show that during intestinal helminth infection, IL-4 derived from Tfh cells is required for IgE class switching and plasmablast formation. Notably, early IgE class switching did not require germinal center formation. Additionally, Tfh cell\u2013derived IL-4 was required to maintain the Th2 response in the mesenteric lymph nodes of infected mice. Collectively, our results indicate that IL-4\u2013producing Tfh cells are central orchestrators of the type 2 immune response in the reactive lymph nodes during parasitic helminth infection.<\/jats:p>","DOI":"10.4049\/jimmunol.1700141","type":"journal-article","created":{"date-parts":[[2017,5,23]],"date-time":"2017-05-23T00:20:25Z","timestamp":1495498825000},"page":"244-252","source":"Crossref","is-referenced-by-count":100,"title":["T Follicular Helper Cell\u2013Derived IL-4 Is Required for IgE Production during Intestinal Helminth Infection"],"prefix":"10.1093","volume":"199","author":[{"given":"Alexandre P","family":"Meli","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Microbiome and Disease Tolerance Centre, McGill University , Montreal, Quebec H3A 2B4,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghislaine","family":"Font\u00e9s","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Microbiome and Disease Tolerance Centre, McGill University , Montreal, Quebec H3A 2B4,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cindy","family":"Leung Soo","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Microbiome and Disease Tolerance Centre, McGill University , Montreal, Quebec H3A 2B4,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irah L","family":"King","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Microbiome and Disease Tolerance Centre, McGill University , Montreal, Quebec H3A 2B4,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,7,1]]},"reference":[{"key":"2025030612090155000_r1","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1007\/s00281-016-0565-1","article-title":"IgE and mast cells in host defense against parasites and venoms","volume":"38","author":"Mukai","year":"2016","journal-title":"Semin. Immunopathol."},{"key":"2025030612090155000_r2","doi-asserted-by":"crossref","first-page":"2335","DOI":"10.4049\/jimmunol.141.7.2335","article-title":"IL-4 is required to generate and sustain in vivo IgE responses","volume":"141","author":"Finkelman","year":"1988","journal-title":"J. Immunol."},{"key":"2025030612090155000_r3","doi-asserted-by":"crossref","first-page":"3206","DOI":"10.4049\/jimmunol.140.9.3206","article-title":"The role of L3T4+ and Lyt-2+ T cells in the IgE response and immunity to Nippostrongylus brasiliensis","volume":"140","author":"Katona","year":"1988","journal-title":"J. Immunol."},{"key":"2025030612090155000_r4","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1038\/ni1128","article-title":"Conditional deletion of Gata3 shows its essential function in TH1-TH2 responses","volume":"5","author":"Zhu","year":"2004","journal-title":"Nat. Immunol."},{"key":"2025030612090155000_r5","first-page":"1","article-title":"Biology of IgE production: IgE cell differentiation and the memory of IgE responses","volume":"388","author":"He","year":"2015","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"2025030612090155000_r6","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1084\/jem.20090313","article-title":"IL-4-producing CD4+ T cells in reactive lymph nodes during helminth infection are T follicular helper cells","volume":"206","author":"King","year":"2009","journal-title":"J. Exp. Med."},{"key":"2025030612090155000_r7","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.immuni.2006.12.006","article-title":"Unique maturation program of the IgE response in vivo","volume":"26","author":"Erazo","year":"2007","journal-title":"Immunity"},{"key":"2025030612090155000_r8","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1084\/jem.20090303","article-title":"T follicular helper cells differentiate from Th2 cells in response to helminth antigens","volume":"206","author":"Glatman Zaretsky","year":"2009","journal-title":"J. Exp. Med."},{"key":"2025030612090155000_r9","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1038\/ni.1715","article-title":"Cytokine-secreting follicular T cells shape the antibody repertoire","volume":"10","author":"Reinhardt","year":"2009","journal-title":"Nat. Immunol."},{"key":"2025030612090155000_r10","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.1084\/jem.20012065","article-title":"Visualization of the genesis and fate of isotype-switched B cells during a primary immune response","volume":"197","author":"Pape","year":"2003","journal-title":"J. Exp. Med."},{"key":"2025030612090155000_r11","doi-asserted-by":"crossref","first-page":"2303","DOI":"10.1084\/jem.183.5.2303","article-title":"Immunoglobulin switch transcript production in vivo related to the site and time of antigen-specific B cell activation","volume":"183","author":"Toellner","year":"1996","journal-title":"J. Exp. Med."},{"key":"2025030612090155000_r12","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1002\/eji.1830220723","article-title":"The murine IgG1\/IgE class switch program","volume":"22","author":"Siebenkotten","year":"1992","journal-title":"Eur. J. Immunol."},{"key":"2025030612090155000_r13","doi-asserted-by":"crossref","first-page":"2755","DOI":"10.1084\/jem.20131539","article-title":"The distinctive germinal center phase of IgE+ B lymphocytes limits their contribution to the classical memory response","volume":"210","author":"He","year":"2013","journal-title":"J. Exp. Med."},{"key":"2025030612090155000_r14","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/j.immuni.2012.02.009","article-title":"Fluorescent in vivo detection reveals that IgE+ B cells are restrained by an intrinsic cell fate predisposition","volume":"36","author":"Yang","year":"2012","journal-title":"Immunity"},{"key":"2025030612090155000_r15","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1084\/jem.20111941","article-title":"Sequential class switching is required for the generation of high affinity IgE antibodies","volume":"209","author":"Xiong","year":"2012","journal-title":"J. Exp. Med."},{"key":"2025030612090155000_r16","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1038\/ni.2256","article-title":"IgE+ memory B cells and plasma cells generated through a germinal-center pathway","volume":"13","author":"Talay","year":"2012","journal-title":"Nat. Immunol."},{"key":"2025030612090155000_r17","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1084\/jem.20102065","article-title":"B cell priming for extrafollicular antibody responses requires Bcl-6 expression by T cells","volume":"208","author":"Lee","year":"2011","journal-title":"J. Exp. Med."},{"key":"2025030612090155000_r18","doi-asserted-by":"crossref","first-page":"2079","DOI":"10.1084\/jem.20120127","article-title":"Distinct cellular pathways select germline-encoded and somatically mutated antibodies into immunological memory","volume":"209","author":"Kaji","year":"2012","journal-title":"J. Exp. Med."},{"key":"2025030612090155000_r19","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-1-4939-2498-1_1","article-title":"Identification of mouse T follicular helper cells by flow cytometry","volume":"1291","author":"Meli","year":"2015","journal-title":"Methods Mol. Biol."},{"key":"2025030612090155000_r20","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.chom.2008.08.014","article-title":"Polyclonal and specific antibodies mediate protective immunity against enteric helminth infection","volume":"4","author":"McCoy","year":"2008","journal-title":"Cell Host Microbe"},{"key":"2025030612090155000_r21","doi-asserted-by":"crossref","first-page":"E5169","DOI":"10.1073\/pnas.1412663111","article-title":"Basophil-mediated protection against gastrointestinal helminths requires IgE-induced cytokine secretion","volume":"111","author":"Schwartz","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025030612090155000_r22","doi-asserted-by":"crossref","first-page":"6138","DOI":"10.4049\/jimmunol.1001703","article-title":"A nonredundant role for IL-21 receptor signaling in plasma cell differentiation and protective type 2 immunity against gastrointestinal helminth infection","volume":"185","author":"King","year":"2010","journal-title":"J. Immunol."},{"key":"2025030612090155000_r23","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.immuni.2005.09.006","article-title":"A two-step process for cytokine production revealed by IL-4 dual-reporter mice","volume":"23","author":"Mohrs","year":"2005","journal-title":"Immunity"},{"key":"2025030612090155000_r24","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/362245a0","article-title":"Disruption of the murine IL-4 gene blocks Th2 cytokine responses","volume":"362","author":"Kopf","year":"1993","journal-title":"Nature"},{"key":"2025030612090155000_r25","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1126\/science.1175870","article-title":"Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation","volume":"325","author":"Johnston","year":"2009","journal-title":"Science"},{"key":"2025030612090155000_r26","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.immuni.2009.07.002","article-title":"The transcriptional repressor Bcl-6 directs T follicular helper cell lineage commitment","volume":"31","author":"Yu","year":"2009","journal-title":"Immunity"},{"key":"2025030612090155000_r27","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1126\/science.1176676","article-title":"Bcl6 mediates the development of T follicular helper cells","volume":"325","author":"Nurieva","year":"2009","journal-title":"Science"},{"key":"2025030612090155000_r28","doi-asserted-by":"crossref","first-page":"3705","DOI":"10.4049\/jimmunol.1300378","article-title":"Insights into the role of Bcl6 in follicular Th cells using a new conditional mutant mouse model","volume":"191","author":"Hollister","year":"2013","journal-title":"J. Immunol."},{"key":"2025030612090155000_r29","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.jaci.2016.04.021","article-title":"Follicular helper T cells mediate IgE antibody response to airborne allergens","volume":"139","author":"Kobayashi","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"2025030612090155000_r30","doi-asserted-by":"crossref","first-page":"2130","DOI":"10.1002\/eji.201344203","article-title":"B-cell-intrinsic STAT6 signaling controls germinal center formation","volume":"44","author":"Turqueti-Neves","year":"2014","journal-title":"Eur. J. Immunol."},{"key":"2025030612090155000_r31","doi-asserted-by":"crossref","first-page":"5099","DOI":"10.4049\/jimmunol.179.8.5099","article-title":"Role of CXCR5 and CCR7 in follicular Th cell positioning and appearance of a programmed cell death gene-1high germinal center-associated subpopulation","volume":"179","author":"Haynes","year":"2007","journal-title":"J. Immunol."},{"key":"2025030612090155000_r32","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1007\/s13238-015-0210-0","article-title":"Phenotypic Tfh development promoted by CXCR5-controlled re-localization and IL-6 from radiation-resistant cells","volume":"6","author":"Chen","year":"2015","journal-title":"Protein Cell"},{"key":"2025030612090155000_r33","doi-asserted-by":"crossref","first-page":"7997","DOI":"10.1038\/ncomms8997","article-title":"Batf is important for IL-4 expression in T follicular helper cells","volume":"6","author":"Sahoo","year":"2015","journal-title":"Nat. Commun."},{"key":"2025030612090155000_r34","doi-asserted-by":"crossref","first-page":"7264","DOI":"10.1128\/MCB.19.10.7264","article-title":"Transcriptional repression of Stat6-dependent interleukin-4-induced genes by BCL-6: specific regulation of iepsilon transcription and immunoglobulin E switching","volume":"19","author":"Harris","year":"1999","journal-title":"Mol. Cell. Biol."},{"key":"2025030612090155000_r35","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.4049\/jimmunol.167.3.1522","article-title":"Differential regulation of mouse germline Ig \u03b31 and \u03b5 promoters by IL-4 and CD40","volume":"167","author":"Mao","year":"2001","journal-title":"J. Immunol."},{"key":"2025030612090155000_r36","doi-asserted-by":"crossref","first-page":"2873","DOI":"10.1084\/jem.20080840","article-title":"ICOS-dependent extrafollicular helper T cells elicit IgG production via IL-21 in systemic autoimmunity","volume":"205","author":"Odegard","year":"2008","journal-title":"J. Exp. Med."},{"key":"2025030612090155000_r37","doi-asserted-by":"crossref","first-page":"5536","DOI":"10.1182\/blood-2008-12-193037","article-title":"The BCL6 transcriptional program features repression of multiple oncogenes in primary B cells and is deregulated in DLBCL","volume":"113","author":"Ci","year":"2009","journal-title":"Blood"},{"key":"2025030612090155000_r38","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2017.01.018","article-title":"Lifelong memory responses perpetuate humoral Th2 immunity and anaphylaxis in patients with food allergy","author":"Jimenez-Saiz","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"2025030612090155000_r39","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1038\/ng0697-161","article-title":"The BCL-6 proto-oncogene controls germinal-centre formation and Th2-type inflammation","volume":"16","author":"Ye","year":"1997","journal-title":"Nat. Genet."},{"key":"2025030612090155000_r40","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1126\/science.276.5312.589","article-title":"Control of inflammation, cytokine expression, and germinal center formation by BCL-6","volume":"276","author":"Dent","year":"1997","journal-title":"Science"},{"key":"2025030612090155000_r41","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.immuni.2015.11.017","article-title":"T follicular helper cell plasticity shapes pathogenic T helper 2 cell-mediated immunity to inhaled house dust mite","volume":"44","author":"Ballesteros-Tato","year":"2016","journal-title":"Immunity"},{"key":"2025030612090155000_r42","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1016\/j.celrep.2016.04.023","article-title":"Lymphotoxin-dependent B cell-FRC crosstalk promotes de novo follicle formation and antibody production following intestinal helminth infection","volume":"15","author":"Dubey","year":"2016","journal-title":"Cell Reports"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/199\/1\/244\/61512292\/ji1700141.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/199\/1\/244\/61512292\/ji1700141.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T13:16:19Z","timestamp":1741266979000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/199\/1\/244\/7962204"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,7,1]]},"references-count":42,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2017,7,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1700141","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2017,7]]},"published":{"date-parts":[[2017,7,1]]}}}