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滤泡辅助T细胞(follicular T-helper cells,TFH)对生发中心反应起着至关重要的调控作用。但是,TFH细胞如何被招募入生发中心以及它们在生发中心内的功能是否受局部微环境影响,仍是悬而未决的问题。在这一研究中,我们发现,生发中心B细胞高表达Ephrin-B1(EFNB1)分子;Ephrin-B1以接触依赖的方式通过TFH细胞上表达的Eph B6受体排斥TFH细胞,抑制抗原特异的TFH-B细胞黏附互作,限制TFH细胞在生发中心的停留时间。另外,Ephrin-B1还通过Eph B4受体促使正在生发中心里的TFH细胞产生白介素-21。于是,在没有了Ephrin-B1的生发中心里,尽管有过量的TFH细胞也无法产生足够的浆细胞;而当Ephrin-B1缺陷型和野生型共存于生发中心,前者会因获得更多TFH黏附依赖的帮助信号而贡献更多骨髓浆细胞。这些结果首次揭示了一个排斥性生发中心导向系统,既参与控制T_(FH)细胞的组织区域特性也调控其辅助功能。
Follicular T-helper cells (TFH) play a crucial regulatory role in germinal center reactions. However, how TFH cells are recruited into germinal centers and whether their function in germinal centers is affected by the local microenvironment remains an open question. In this study, we found that germinal center B cells overexpress Ephrin-B1 (EFNB1) molecules; Ephrin-B1 inhibits TFH cells by Eph B6 receptors expressed on TFH cells in a contact-dependent manner, inhibiting antigen-specific TFH B cell adhesion interaction, limiting TFH cell residence time in the germinal center. In addition, Ephrin-B1 also induces interleukin-21 production in TFH cells in the germinal center via the Eph B4 receptor. Thus, in the absence of Ephrin-B1 in the germinal center, despite excessive TFH cells can not produce enough plasma cells; and when Ephrin-B1-deficient and wild-type co-exist in the germinal center, the former due to get more TFH adhesion Dependent on the help signal and contribute more bone marrow plasma cells. These results revealed, for the first time, an exclusionary germinal center-directed system that participates in controlling the regional properties of T_ (FH) cells as well as regulating its ancillary functions.