IL-21 has a critical role in establishing germinal centers by amplifying early B cell proliferation

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

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13 Citations (Scopus)


The proliferation and differentiation of antigen-specific B cells, including the generation of germinal centers (GC), are prerequisites for long-lasting, antibody-mediated immune protection. Affinity for antigen determines B cell recruitment, proliferation, differentiation, and competitiveness in the response, largely through determining access to T cell help. However, how T cell-derived signals contribute to these outcomes is incompletely understood. Here, we report how the signature cytokine of follicular helper T cells, IL-21, acts as a key regulator of the initial B cell response by accelerating cell cycle progression and the rate of cycle entry, increasing their contribution to the ensuing GC. This effect occurs over a wide range of initial B cell receptor affinities and correlates with elevated AKT and S6 phosphorylation. Moreover, the resultant increased proliferation can explain the IL-21-mediated promotion of plasma cell differentiation. Collectively, our data establish that IL-21 acts from the outset of a T cell-dependent immune response to increase cell cycle progression and fuel cyclic re-entry of B cells, thereby regulating the initial GC size and early plasma cell output.

Original languageEnglish
Article numbere54677
Number of pages15
JournalEMBO Reports
Issue number9
Publication statusPublished - 8 Jul 2022


  • B cells
  • cell cycle
  • germinal center
  • IL-21
  • plasma cells

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