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

Authors:

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

Details:

Immunity, Volume 55, Issue 8, 2022-08-09

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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.