GC-Tfh cell differentiation

项目摘要 CD4T滤泡辅助性细胞(TFH)是生发中心(GC)应答和长期免疫应答所必需的细胞。 长期体液免疫。已有研究提出TFH细胞分化是一个多阶段的过程。 包括PD-1 CXCR5前TFH和PD-1hiCXCR5 Hi生发中心TFH(GC-TFH)细胞的步骤。 然而，大多数研究都使用了广义的“CXCR5 Tfh”细胞，它开始 变得过于简单化，可能会导致混淆--特别是关于GC-TFH细胞分化 和记忆。 树突状细胞激活原始的CD4T细胞并启动TFH细胞分化，包括 诱导CXCR5的表达。GC-Tfh细胞的进一步分化需要与B细胞相互作用 细胞。我们的初步结果表明，前Tfh细胞经历的不是简单的维护 大量进一步分化为GC-Tfh细胞。然而，在很大程度上，人们对此知之甚少 关于这种前TFH向GC-TFH转变的机制。在本应用程序中，我们的目标是 发现Tfh前向GC-Tfh细胞分化过程中的新调节因子。同时，我们还将建立新的 研究GC-TFH记忆的模型系统。我们的提案有可能提供重要的 传染病治疗中如何控制体液免疫反应的知识， 自身免疫性疾病，并帮助针对新的大流行威胁的疫苗开发。

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.