Ephrin-B1调控生发中心T细胞的运动区域与辅助功能

Ephrin-B1-Mediated Regulation of Germinal Center T-Cell Territoriality and Function

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（TFH） cells play a crucial role in orchestrating the germinal center（GC） response. It is not clear whether and how their recruitment and helper functions are regulated locally. We have found GC-expressed Ephrin-B1（EFNB1） serves as a contact-dependent, repulsive guidance cue that signals through TFH-expressed Eph B6 receptor to inhibit T-B adhesion and GC retention of TFH cells. EFNB1 also signals through Eph B4 and Eph B6 to promote interleukin-21（IL-21） production. As a result, EFNB1-null GCs are defective in producing plasma cells despite harboring excessive TFH cells, whereas in a competitive GC reaction EFNB1-deficient B cells produce more bone-marrow plasma cells as a result of gaining more contact-dependent T cell help. These results reveal a new layer of self-organizing regulatory mechanisms for the GC reaction locally.