B and T cells collaborate in antiviral responses via IL-6, IL-21, and transcriptional activator and coactivator, Oct2 and OBF-1.
B and T cells collaborate in antiviral responses via IL-6, IL-21, and transcriptional activator and coactivator, Oct2 and OBF-1.
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DOI：
10.1084/jem.20111504
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发表时间：
2012-10-22
期刊：
影响因子：
--
通讯作者：
Corcoran LM
中科院分区：
文献类型：
--
作者：
Karnowski A;Chevrier S;Belz GT;Mount A;Emslie D;D'Costa K;Tarlinton DM;Kallies A;Corcoran LM
转录激活因子Oct 2和辅因子OBF-1调节B细胞IL-6以诱导T细胞产生IL-21，从而支持Tfh细胞在抗病毒免疫中的发育。对感染的强烈体液应答需要几种造血细胞类型的协作，这些造血细胞类型通过抗原呈递、表面共受体及其配体和分泌因子进行通信。促炎细胞因子IL-6已显示在免疫应答期间促进活化的CD 4 + T细胞分化成T滤泡辅助细胞（TFH细胞）。在T细胞依赖性抗体应答期间，TFH细胞与B细胞合作形成生发中心（GC），部分通过分泌关键细胞因子如IL-21。在这项研究中，我们证明了IL-6或IL-21的损失对TFH细胞的产生和对急性病毒感染反应期间GC的形成具有边际影响。然而，缺乏IL-6和IL-21的小鼠不能产生强有力的TFH细胞依赖性免疫应答。我们发现引流淋巴结中滤泡B细胞中IL-6的产生是抗病毒应答过程中的重要早期事件，并且B细胞衍生的IL-6是体外诱导CD 4 + T细胞产生IL-21和支持体内TFH细胞发育所必需和足够的。最后，转录激活因子Oct 2及其辅因子OBF-1被鉴定为B细胞中IL 6表达的调节因子。
Transcriptional activator Oct2 and cofactor OBF-1 regulate B cell IL-6 to induce T cell production of IL-21, to support Tfh cell development in antiviral immunity. A strong humoral response to infection requires the collaboration of several hematopoietic cell types that communicate via antigen presentation, surface coreceptors and their ligands, and secreted factors. The proinflammatory cytokine IL-6 has been shown to promote the differentiation of activated CD4+ T cells into T follicular helper cells (TFH cells) during an immune response. TFH cells collaborate with B cells in the formation of germinal centers (GCs) during T cell–dependent antibody responses, in part through secretion of critical cytokines such as IL-21. In this study, we demonstrate that loss of either IL-6 or IL-21 has marginal effects on the generation of TFH cells and on the formation of GCs during the response to acute viral infection. However, mice lacking both IL-6 and IL-21 were unable to generate a robust TFH cell–dependent immune response. We found that IL-6 production in follicular B cells in the draining lymph node was an important early event during the antiviral response and that B cell–derived IL-6 was necessary and sufficient to induce IL-21 from CD4+ T cells in vitro and to support TFH cell development in vivo. Finally, the transcriptional activator Oct2 and its cofactor OBF-1 were identified as regulators of Il6 expression in B cells.
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影响因子：
32.4
作者：
Choi YS;Kageyama R;Eto D;Escobar TC;Johnston RJ;Monticelli L;Lao C;Crotty S
通讯作者：
Crotty S
DOI：
10.1084/jem.20081571
发表时间：
2009-01-16
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Dienz O;Eaton SM;Bond JP;Neveu W;Moquin D;Noubade R;Briso EM;Charland C;Leonard WJ;Ciliberto G;Teuscher C;Haynes L;Rincon M
通讯作者：
Rincon M
影响因子：
4.4
作者：
Corcoran, LM;Koentgen, F;Humbert, PO
通讯作者：
Humbert, PO
影响因子：
11.4
作者：
Brunner, Cornelia;Sindrilaru, Anca;Wirth, Thomas
通讯作者：
Wirth, Thomas
影响因子：
20.3
作者：
Eddahri, Fouad;Denanglaire, Sebastien;Andris, Fabienne
通讯作者：
Andris, Fabienne