Interleukin-21, acting beyond the immunological synapse, independently controls T follicular helper and germinal center B cells

Isaak Quast, Alexandra R. Dvorscek, Celine Pattaroni, Thiago M. Steiner, Craig I. McKenzie, Catherine Pitt, Kristy O'Donnell, Zhoujie Ding, Danika L. Hill, Robert Brink, Marcus J. Robinson, Dimitra Zotos, David M. Tarlinton

Research output: Contribution to journalArticleResearchpeer-review

22 Citations (Scopus)


Germinal centers (GCs), transient structures within B cell follicles and central to affinity maturation, require the coordinated behavior of T and B cells. IL-21, a pleiotropic T cell-derived cytokine, is key to GC biology through incompletely understood mechanisms. By genetically restricting production and receipt of IL-21 in vivo, we reveal how its independent actions on T and B cells combine to regulate the GC. IL-21 established the magnitude of the GC B cell response by promoting CD4+ T cell expansion and differentiation in a dose-dependent manner and with paracrine activity. Within GC, IL-21 specifically promoted B cell centroblast identity and, when bioavailability was high, plasma cell differentiation. Critically, these actions may occur irrespective of cognate T-B interactions, making IL-21 a general promoter of growth as distinct to a mediator of affinity-driven selection via synaptic delivery. This promiscuous activity of IL-21 explains the consequences of IL-21 deficiency on antibody-based immunity.

Original languageEnglish
Pages (from-to)1414-1430.e5
Number of pages23
Issue number8
Publication statusPublished - 9 Aug 2022


  • affinity maturation
  • B cell memory
  • germinal centers
  • humoral immunity
  • interleukin 21
  • T follicular helper cells

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