Département Immunologie, Inflammation, et Infection, Institut Cochin, INSERM, U1016, CNRS, UMR8104, Université de Paris, F-75014 Paris, France;
Dr. Senckenberg Institute of Pathology, Goethe University, 60590 Frankfurt am Main, Germany.
J Immunol. 2020 Sep 1;205(5):1248-1255. doi: 10.4049/jimmunol.1901475. Epub 2020 Jul 22.
T follicular helper (Tfh) cells play a very important role in mounting a humoral response. Studies conducted in mouse models have revealed with good kinetic and spatial resolution the dynamics of these cells in germinal centers (GC) and their cross-talk with B cells upon an immune response. However, whether a similar migratory behavior is performed by human Tfh cells is unclear, as technology to track them in situ has been lacking. In this study, we combined traditional immunohistochemistry and real-time fluorescent imaging approaches on fresh human adenoid slices to provide static and dynamic information on Tfh cells. Our data indicate that GC light zones are composed of two distinct areas in terms of Tfh cell distribution and migration. In the outer GC light zones, Tfh cells migrate actively and with a high ability to form dynamic clusters showing intense and rapid reorganization. In these outer regions, Tfh cells demonstrate multiple interactions between each other. Conversely, in central regions of GC light zones, Tfh cells are much more static, forming long-lasting conjugates. These findings reveal for the first time, to our knowledge, the dynamic behavior whereby Tfh cells migrate in human GC and highlight the heterogeneity of GC for Tfh cell motility.
滤泡辅助 T 细胞（Tfh）在体液免疫反应中发挥着非常重要的作用。在小鼠模型中的研究已经以良好的动力学和空间分辨率揭示了这些细胞在生发中心（GC）中的动态变化，以及它们在免疫反应中与 B 细胞的相互作用。然而，人类 Tfh 细胞是否表现出类似的迁移行为尚不清楚，因为缺乏跟踪它们的原位技术。在这项研究中，我们结合传统的免疫组织化学和实时荧光成像方法，对新鲜的人腺样体切片进行研究，提供了 Tfh 细胞的静态和动态信息。我们的数据表明，GC 亮区在 Tfh 细胞的分布和迁移方面由两个不同的区域组成。在外 GC 亮区，Tfh 细胞表现出活跃的迁移，具有形成动态聚集体的高能力，表现出强烈和快速的重组。在这些外区，Tfh 细胞之间存在多种相互作用。相反，在 GC 亮区的中心区域，Tfh 细胞则更加静止，形成持久的结合体。这些发现首次揭示了 Tfh 细胞在人类 GC 中的迁移动态行为，并突出了 GC 对 Tfh 细胞迁移的异质性。
