First Author | Quast I | Year | 2022 |
Journal | Immunity | Volume | 55 |
Issue | 8 | Pages | 1414-1430.e5 |
PubMed ID | 35896116 | Mgi Jnum | J:330818 |
Mgi Id | MGI:7332692 | Doi | 10.1016/j.immuni.2022.06.020 |
Citation | Quast I, et al. (2022) Interleukin-21, acting beyond the immunological synapse, independently controls T follicular helper and germinal center B cells. Immunity 55(8):1414-1430.e5 |
abstractText | 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. |