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T cell help in the germinal center: homing in on the role of IL-21

Petersone, Lina; Walker, Lucy SK; (2024) T cell help in the germinal center: homing in on the role of IL-21. International Immunology 10.1093/intimm/dxad056. (In press). Green open access

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Abstract

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 GC master transcription factor 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, recent studies have now revealed how IL-21 signal strength shapes the fate choice between GC cycle reentry and antibody secreting cell 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.

Type: Article
Title: T cell help in the germinal center: homing in on the role of IL-21
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/intimm/dxad056
Publisher version: http://dx.doi.org/10.1093/intimm/dxad056
Language: English
Additional information: © The Author(s) 2024. Published by Oxford University Press on behalf of The Japanese Society for Immunology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/).
Keywords: B cells, autoimmunity, follicular helper T cells (Tfh), humoral immunity
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: https://discovery.ucl.ac.uk/id/eprint/10185916
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