GC-Tfh cell differentiation

项目概要 CD4 T 滤泡辅助 (Tfh) 细胞对于生发中心 (GC) 反应和长期免疫反应至关重要。 术语“体液免疫”。有人提出，Tfh 细胞分化是一个多阶段过程， 包括 PD-1 CXCR5 pre-Tfh 和 PD-1hiCXCR5hi 生发中心 Tfh (GC-Tfh) 细胞的步骤。 然而，大多数研究一直在使用广泛定义的“CXCR5 Tfh”细胞，该细胞开始 变得过于简单化并可能导致混乱——特别是关于 GC-Tfh 细胞分化 和记忆。 树突状细胞激活幼稚 CD4 T 细胞并启动 Tfh 细胞分化，包括 CXCR5表达的诱导。 GC-Tfh 细胞的进一步分化需要与 B 相互作用 细胞。我们的初步结果表明，前 Tfh 细胞不是进行简单的维护，而是进行 显着进一步分化成为GC-Tfh细胞。但在很大程度上，人们知之甚少 关于 Tfh 前到 GC-Tfh 转变的潜在机制。在这个应用程序中，我们的目标是 鉴定 Tfh 前到 GC-Tfh 细胞分化的新调节因子。同时，我们还将建立新的 研究 GC-Tfh 内存的模型系统。我们的建议有可能提供重要的 有关如何控制体液免疫反应以治疗传染病的知识， 自身免疫性疾病，并帮助开发针对新的大流行威胁的疫苗。

Project Summary CD4+ T follicular helper (Tfh) cells are essential for germinal center (GC) responses and long- term humoral immunity. It has been proposed that Tfh cell differentiation is a multi-stage process that includes steps of PD-1+CXCR5+ pre-Tfh and PD-1hiCXCR5hi germinal center Tfh (GC-Tfh) cells. However, most studies have been using the broadly defined “CXCR5+ Tfh” cells, which starts to become too simplistic and may lead to confusion—particularly regarding the GC-Tfh cell differentiation and memory. Dendritic cells activate naïve CD4+ T cells and initiate Tfh cell differentiation including the induction of CXCR5 expression. The further GC-Tfh cell differentiation requires interactions with B cells. Our preliminary results suggest that instead of simple maintenance, pre-Tfh cells undergo substantial further differentiation to become GC-Tfh cells. To a large extent, however, little is known about the mechanism underlying this pre-Tfh to GC-Tfh transition. In this application, we aim to identify novel regulators in pre-Tfh to GC-Tfh cell differentiation. Meanwhile, we will also establish new model systems to study GC-Tfh memory. Our proposal has the potential to provide important knowledge on how to control the humoral immune response for the treatment of infectious diseases, autoimmune disorders, and to aid vaccine development for new pandemic threats.