{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:05:51Z","timestamp":1792785951577,"version":"4.5.0"},"reference-count":102,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2024,1,2]],"date-time":"2024-01-02T00:00:00Z","timestamp":1704153600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Wellcome Investigator","award":["220772\/Z\/20\/Z"],"award-info":[{"award-number":["220772\/Z\/20\/Z"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,2,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Interleukin 21 (IL-21) is a pleiotropic cytokine that is overproduced in multiple autoimmune settings. Provision of IL-21 from follicular helper T cells is an important component of T-cell help within germinal centers (GC), and the last few years have seen a resurgence of interest in IL-21 biology in the context of the GC environment. While it has been more than a decade since T cell-derived IL-21 was found to upregulate B-cell expression of the GC master transcription factor B-cell lymphoma 6 (Bcl-6) and to promote GC expansion, several recent studies have collectively delivered significant new insights into how this cytokine shapes GC B-cell selection, proliferation, and fate choice. It is now clear that IL-21 plays an important role in GC zonal polarization by contributing to light zone GC B-cell positive selection for dark zone entry as well as by promoting cyclin D3-dependent dark zone inertial cycling. While it has been established that IL-21 can contribute to the modulation of GC output by aiding the generation of antibody-secreting cells (ASC), recent studies have now revealed how IL-21 signal strength shapes the fate choice between GC cycle re-entry and ASC differentiation in vivo. Both provision of IL-21 and sensitivity to this cytokine are finely tuned within the GC environment, and dysregulation of this pathway in autoimmune settings could alter the threshold for germinal center B-cell selection and differentiation, potentially promoting autoreactive B-cell responses.<\/jats:p>","DOI":"10.1093\/intimm\/dxad056","type":"journal-article","created":{"date-parts":[[2023,12,30]],"date-time":"2023-12-30T11:07:17Z","timestamp":1703934437000},"page":"89-98","source":"Crossref","is-referenced-by-count":17,"title":["T-cell help in the germinal center: homing in on the role of IL-21"],"prefix":"10.1093","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8571-9185","authenticated-orcid":false,"given":"Lina","family":"Petersone","sequence":"first","affiliation":[{"name":"University College London Division of Infection and Immunity, Institute of Immunity and Transplantation, Pears Building, Royal Free Campus , London NW3 2PP , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5986-5015","authenticated-orcid":false,"given":"Lucy S K","family":"Walker","sequence":"additional","affiliation":[{"name":"University College London Division of Infection and Immunity, Institute of Immunity and Transplantation, Pears Building, Royal Free Campus , London NW3 2PP , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,1,2]]},"reference":[{"key":"2024022117270558400_CIT0001","first-page":"57","article-title":"Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function","volume-title":"Nature","author":"Parrish-Novak","year":"2000"},{"key":"2024022117270558400_CIT0002","first-page":"11439","article-title":"Cloning of a type I cytokine receptor most related to the IL-2 receptor beta chain","volume-title":"Proc Natl Acad Sci 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