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细胞被认为是幼稚B细胞，类别转换细胞被认为是记忆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+ CD 27 + B细胞），它们也携带突变的V基因。有争议地讨论了这些细胞是否是生发中心（GC）衍生的记忆B细胞，它们是否衍生自T细胞非依赖性免疫应答，或者它们是否在抗原非依赖性初级多样化过程中产生。我们的目的是澄清的起源和功能的两个突变的IgM表达B细胞亚群。在该项目的第一部分，我们表明，突变的IgM+ B细胞在表型上更类似于类别转换记忆，而不是幼稚的B细胞，IgM+ B细胞在边缘区没有经历体细胞超突变。我们从B细胞亚群的基因芯片分析开始。首次发现IgM+IgD+ GC B细胞可能是突变IgM+ B细胞的来源。在本发明中，我们计划a）研究四种主要B细胞亚群的差异基因表达，以揭示突变的IgM+ B细胞的起源和特异性功能，B）用B细胞亚群进行体外研究，以证实它们的特异性功能，c）分析突变的IgM+ B细胞中作为GC衍生物的分子特征的Bcl-6基因突变，d）继续对IgM+IgD+ GC B细胞进行分子分析，以及e）对异常的“仅IgD”B细胞群体进行分子表征。