小柯机器人

澳大利亚莫纳什大学David M. Tarlinton和Isaak Quast共同合作近期取得重要工作进展，他们研究揭示了白细胞介素-21作用于免疫突触之外，独立控制T滤泡辅助细胞和生发中心B细胞。该项研究成果2022年7月26日在线出版于《免疫学》杂志上。

IL-21是一种多效性 T 细胞来源的细胞因子，通过不完全理解的机制成为GC生物学的关键。通过在体内基因限制IL-21的产生和接收，研究人员揭示了IL-21对T细胞和B细胞的独立作用如何结合起来调节GC。IL-21通过促进CD4⁺T细胞的扩张和分化，以剂量依赖的方式和旁分泌活性建立了GC B细胞反应的规模。在GC中，在GC内，IL-21特异性地促进了B细胞中心细胞的特性，当生物利用度高时，浆细胞的分化也得到了促进。

至关重要的是，这些行为可能与同源T-B相互作用无关，这使得IL-21成为一种一般的生长促进因子，而不是通过突触传递的亲和力驱动的选择媒介。IL-21的这种混杂活性解释了IL-21缺乏对基于抗体的免疫的后果。

据介绍，生发中心 (GC)是B细胞滤泡内的瞬时结构和亲和力成熟的中心，需要T细胞和B细胞的协调行为。

附：英文原文

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

Author: 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

Issue&Volume: 2022-07-26

Abstract: Germinal centers (GCs), transient structures within B cell follicles and central toaffinity maturation, require the coordinated behavior of T and B cells. IL-21, a pleiotropicT 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 paracrineactivity. Within GC, IL-21 specifically promoted B cell centroblast identity and,when bioavailability was high, plasma cell differentiation. Critically, these actionsmay occur irrespective of cognate T-B interactions, making IL-21 a general promoterof 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 onantibody-based immunity.

DOI: 10.1016/j.immuni.2022.06.020

Source: https://www.cell.com/immunity/fulltext/S1074-7613(22)00293-X

Immunity：《免疫》，创刊于1994年。隶属于细胞出版社，最新IF：43.474
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