2. Academic Validation
  3. IL-21 shapes germinal center polarization via light zone B cell selection and cyclin D3 upregulation

IL-21 shapes germinal center polarization via light zone B cell selection and cyclin D3 upregulation

  • J Exp Med. 2023 Oct 2;220(10):e20221653. doi: 10.1084/jem.20221653.
Lina Petersone 1,  Chun Jing Wang 1,  Natalie M Edner 1,  Astrid Fabri 1,  Spyridoula-Angeliki Nikou 1,  Claudia Hinze 1,  Ellen M Ross 1,  Elisavet Ntavli 1,  Yassin Elfaki 1,  Frank Heuts 1,  Vitalijs Ovcinnikovs 1,  Andrea Rueda Gonzalez 1,  Luke P Houghton 1,  Hannah M Li 1,  Yang Zhang 2,  Kai-Michael Toellner 2,  Lucy S K Walker 1
Affiliations

Affiliations

  • 1 Division of Infection and Immunity, Institute of Immunity and Transplantation, University College London , London, UK.
  • 2 Institute of Immunology and Immunotherapy, University of Birmingham , Birmingham, UK.
PMID: 37466652 DOI: 10.1084/jem.20221653
Abstract

Germinal center (GC) dysregulation has been widely reported in the context of autoimmunity. Here, we show that interleukin 21 (IL-21), the archetypal follicular helper T cell (Tfh) cytokine, shapes the scale and polarization of spontaneous chronic autoimmune as well as transient immunization-induced GC. We find that IL-21 receptor deficiency results in smaller GC that are profoundly skewed toward a LIGHT zone GC B cell phenotype and that IL-21 plays a key role in selection of LIGHT zone GC B cells for entry to the dark zone. LIGHT zone skewing has been previously reported in mice lacking the cell cycle regulator cyclin D3. We demonstrate that IL-21 triggers cyclin D3 upregulation in GC B cells, thereby tuning dark zone inertial cell cycling. Lastly, we identify Foxo1 regulation as a link between IL-21 signaling and GC dark zone formation. These findings reveal new biological roles for IL-21 within GC and have implications for autoimmune settings where IL-21 is overproduced.

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