Phänotypische, genetische und funktionelle Charakterisierung humaner Gedächtnis-B-Zell-Subpopulationen

人类记忆 B 细胞亚群的表型、遗传和功能特征

• 批准号: 5447828
• 负责人: Professor Dr. Ralf Küppers
• 金额: --
• 依托单位: Institut für Zellbiologie (Tumorforschung)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2005
• 资助国家: 德国
• 起止时间: 2004-12-31 至 2007-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5447828?language=en
• 关键词: Ph; notypische; genetische; und; funktionelle

Traditionally, IgM+IgD+ B cells were considered as naive B cells and class-switched cells as memory B cells. We described two IgM-expressing B cell subsets (IgM+IgD- (IgM-only) and IgM+IgD+CD27+ B cells) that also carry mutated V genes. It is controversely discussed whether these cells are germinal centre (GC)-derived memory B cells, they derive from T cell-independent immune responses or they are generated in an antigen-independent primary diversification process. We aim to clarify the origin and functions of the two mutated IgM-expressing B cell subsets. In the first part of the project, we showed that the mutated IgM+ B cells are phenotypically more similar to class-switched memory than to naïve B cells and that IgM+ B cells are not undergoing somatic hypermutation in the marginal zone. We began with a genechip analysis of the B cell subsets. First indication was obtained that IgM+IgD+ GC B cells may be the origin of the mutated IgM+ B cells. In the present proposal we plan to a) study differential gene expression of the four main B cell subsets to reveal the origin and specific functions of the mutated IgM+ B cells, b) perform in vitro studies with the B cell subsets to characterise their specific functions, c) analyse the mutated IgM+ B cells for mutations in the Bcl-6 gene as a molcular trait of a GC derivation, d) continue the molecular analysis of IgM+IgD+ GC B cells, and e) perform a molecular characterization of an unusal population of “IgD-only” B cells.

传统上，IgM+IgD+ B 细胞被视为幼稚 B 细胞，类别转换细胞被视为记忆 B 细胞。我们描述了两种表达 IgM 的 B 细胞亚群（IgM+IgD-（仅 IgM）和 IgM+IgD+CD27+ B 细胞），它们也携带突变的 V 基因。关于这些细胞是生发中心 (GC) 衍生的记忆 B 细胞、源自 T 细胞独立的免疫反应还是在不依赖抗原的初级多样化过程中产生，存在争议。我们的目标是阐明两种表达 IgM 的突变 B 细胞亚群的起源和功能。在该项目的第一部分中，我们表明突变的 IgM+ B 细胞在表型上与类别转换记忆比幼稚 B 细胞更相似，并且 IgM+ B 细胞在边缘区没有经历体细胞超突变。我们首先对 B 细胞亚群进行基因芯片分析。第一个迹象表明，IgM+IgD+ GC B 细胞可能是突变的 IgM+ B 细胞的起源。在本提案中，我们计划 a) 研究四种主要 B 细胞亚群的差异基因表达，以揭示突变 IgM+ B 细胞的起源和特定功能，b) 对 B 细胞亚群进行体外研究，以表征其特定功能，c) 分析突变 IgM+ B 细胞中 Bcl-6 基因的突变，作为 GC 衍生的分子特征，d) 继续进行以下分子分析： IgM+IgD+ GC B 细胞，以及 e) 对异常的“仅 IgD”B 细胞群进行分子表征。