Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China.
Laboratory of Dynamic Immunobiology, Institute for Immunology, Tsinghua University, Beijing 100084, China.
Science. 2017 May 19;356(6339). doi: 10.1126/science.aai9264. Epub 2017 Apr 13.
Follicular T helper (T) cells orchestrate the germinal center (GC) reaction locally. Local mechanisms regulating their dynamics and helper functions are not well defined. Here we found that GC-expressed ephrin B1 (EFNB1) repulsively inhibited T cell to B cell adhesion and GC T retention by signaling through T-expressed EPHB6 receptor. At the same time, EFNB1 promoted interleukin-21 production from GC T cells by signaling predominantly through EPHB4. Consequently, EFNB1-null GCs were associated with defective production of plasma cells despite harboring excessive T cells. In a competitive GC reaction, EFNB1-deficient B cells more efficiently interacted with T cells and produced more bone-marrow plasma cells, likely as a result of gaining more contact-dependent help. Our results reveal a contact-dependent repulsive guidance system that controls GC T dynamics and effector functions locally.
滤泡辅助 T 细胞（Tfh）在局部协调生发中心（GC）反应。局部调节其动力学和辅助功能的机制尚未明确。我们发现，GC 表达的 EphrinB1（EFNB1）通过信号转导抑制 T 细胞与 B 细胞的黏附和 GC T 细胞的保留，该信号转导通过 T 细胞表达的 EPHB6 受体进行。同时，EFNB1 通过信号转导主要通过 EPHB4 促进 GC T 细胞产生白细胞介素-21。因此，尽管 EFNB1 缺失的 GC 中含有过多的 T 细胞，但浆细胞的产生仍然存在缺陷。在竞争性 GC 反应中，EFNB1 缺失的 B 细胞与 T 细胞更有效地相互作用，并产生更多的骨髓浆细胞，这可能是由于获得了更多的接触依赖性帮助。我们的结果揭示了一种接触依赖性的排斥性制导系统，该系统可局部控制 GC T 细胞的动力学和效应功能。
