Moriyama Saya, Takahashi Noriko, Green Jesse A, Hori Shohei, Kubo Masato, Cyster Jason G, Okada Takaharu
Laboratory for Tissue Dynamics, Laboratory for Lymphocyte Differentiation, Laboratory for Immune Homeostasis, and Laboratory for Cytokine Regulation, RCAI, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Yokohama, Kanagawa 230-0045, JapanLaboratory for Tissue Dynamics, Laboratory for Lymphocyte Differentiation, Laboratory for Immune Homeostasis, and Laboratory for Cytokine Regulation, RCAI, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Yokohama, Kanagawa 230-0045, Japan Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan.
Laboratory for Tissue Dynamics, Laboratory for Lymphocyte Differentiation, Laboratory for Immune Homeostasis, and Laboratory for Cytokine Regulation, RCAI, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Yokohama, Kanagawa 230-0045, Japan.
J Exp Med. 2014 Jun 30;211(7):1297-305. doi: 10.1084/jem.20131666. Epub 2014 Jun 9.
Follicular helper T (Tfh) cells access the B cell follicle to promote antibody responses and are particularly important for germinal center (GC) reactions. However, the molecular mechanisms of how Tfh cells are physically associated with GCs are incompletely understood. We report that the sphingosine-1-phosphate receptor 2 (S1PR2) gene is highly expressed in a subpopulation of Tfh cells that localizes in GCs. S1PR2-deficient Tfh cells exhibited reduced accumulation in GCs due to their impaired retention. T cells deficient in both S1PR2 and CXCR5 were ineffective in supporting GC responses compared with T cells deficient only in CXCR5. These results suggest that S1PR2 and CXCR5 cooperatively regulate localization of Tfh cells in GCs to support GC responses.
滤泡辅助性T（Tfh）细胞进入B细胞滤泡以促进抗体反应，对生发中心（GC）反应尤为重要。然而，Tfh细胞与GC在物理上如何关联的分子机制尚未完全明确。我们报告称，鞘氨醇-1-磷酸受体2（S1PR2）基因在定位于GC的Tfh细胞亚群中高表达。缺乏S1PR2的Tfh细胞因滞留受损而在GC中的积累减少。与仅缺乏CXCR5的T细胞相比，同时缺乏S1PR2和CXCR5的T细胞在支持GC反应方面无效。这些结果表明，S1PR2和CXCR5协同调节Tfh细胞在GC中的定位以支持GC反应。
