Department of Basic Biomedical Sciences, School of Medicine, Laboratory of Dynamic Immunobiology, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, China.
Immunol Rev. 2019 Mar;288(1):28-36. doi: 10.1111/imr.12747.
Follicular T-helper (T ) cells play a crucial role in three aspects of the germinal center (GC) response. They promote GC formation, arbitrate competition among GC B cells to determine the outcome of affinity maturation, and regulate GC output of memory and plasma cells to shape the long-lived humoral immune memory. Of fundamental importance are dynamic physical interactions between T and B cells, which are the main platform for T cells to deliver "help" factors to B cells and also for reciprocal signaling from B cells to maintain the helper state of T cells. Recent work has significantly expanded our understanding of how T-B interactions are spatiotemporally regulated and molecularly orchestrated to fulfill those T functions. In this review, we elaborate two modes of T-B interactions, the antigen-specific or cognate mode in which T cells engage individual antigen-presenting B cells and the antigen nonspecific bystander mode in which T cells are engaged with the ensemble of follicular B cells. We discuss findings that indicate how short-lived cognate T-B contacts coupled with an intercellular positive feedback drive affinity-based selection and how bystander interactions between T and B cells regulate follicular T-cell recruitment and maintenance of an appropriate helper state. We argue that this combination of bystander and cognate interactions with B cells constantly shapes the internal state of T cells and provides the platform to execute their helper functions.
滤泡辅助性 T 细胞（Tfh）在生发中心（GC）反应的三个方面发挥着关键作用。它们促进 GC 的形成，仲裁 GC B 细胞之间的竞争，以决定亲和力成熟的结果，并调节 GC 中记忆和浆细胞的输出，从而塑造长期的体液免疫记忆。至关重要的是 T 细胞和 B 细胞之间的动态物理相互作用，这是 T 细胞向 B 细胞传递“帮助”因子的主要平台，也是 B 细胞发出信号以维持 T 细胞辅助状态的主要平台。最近的研究工作极大地扩展了我们对 T-B 相互作用如何在时空上受到调控以及分子上协调以实现这些 T 功能的理解。在这篇综述中，我们详细阐述了两种 T-B 相互作用模式，即 T 细胞与单个抗原呈递 B 细胞的抗原特异性或同源模式，以及 T 细胞与滤泡 B 细胞整体的抗原非特异性旁观者模式。我们讨论了一些发现，这些发现表明短暂的同源 T-B 接触与细胞间正反馈相结合如何驱动基于亲和力的选择，以及 T 和 B 细胞之间的旁观者相互作用如何调节滤泡 T 细胞的募集和辅助状态的维持。我们认为，这种与 B 细胞的旁观者和同源相互作用的组合不断塑造 T 细胞的内部状态，并为执行其辅助功能提供了平台。
