B Cell Distribution, Differentiation and Diversity in Tissues

该项目的广泛目标是利用一种独特而新颖的共享资源--从 器官捐献者--确定正常人免疫中B细胞亚群、B细胞亚群和反应的特征 系统。我们将强调组织驻留细胞，包括淋巴组织中的驻留细胞，以及粘膜中驻留的细胞 和实质组织。该项目的第一个目标是使用流式细胞术和免疫组织学。 分析综合确定急性淋巴细胞白血病B系细胞的表型、亚群和特征 上面的纸巾。除了发现新的B细胞亚群--一个主要终点--之外，这项努力还将 提供人类独一无二的B细胞图谱，并将极大地帮助相关和解释数据 PBL，这通常是人类受试者唯一可用的样本。第二个目标是用来定义基因 在工作的第一部分中确定的关键人群的表达谱。这将证实 表型子集的定义，允许不同类型的相似子集之间有意义的比较 组织以及组织特异性适应的定义(例如，组织特异性趋化因子受体或 其他类似类型的B细胞中的另一种)。它还将提供对两者的功能的许多见解 新发现和以前已知的B细胞类型；基因表达和表型将使比对 通过更好地研究类似的小鼠细胞类型，加强人类和小鼠的工作。再说一遍， 将产生大量对几乎所有人类免疫研究有用的信息。最后，我们将带着 淋巴细胞的独特性质的优势-克隆性VDJ重排-特别是B细胞- 体细胞超突变--从静态分析中获得动态图像。这将被启用 通过指数级扩展的能力

The broad goal of this Project is to utilize a unique and novel shared resource-access to fresh tissue from organ donors-to characterize B cell compartments, subsets, and responses in the normal human immune system. We will emphasize tissue-resident cells, including in lymphoid tissue, and cells resident in mucosal and parenchymal tissues. The first goal of the project is to use flow cytometric and immunohlstologic analysis to comprehensively determine the phenotypes, subsets, and characteristics of B lineage cells in all of the above tissues. In addition to the discovery of new B cell subsets-a major endpoint-this effort will provide a unique atlas of B cells in the human, and will greatly aid correlation and interpretation of data on PBL, which is often the only available sample from human subjects. The second goal is to use to define gene expression profiles of key populations identified in the first part of the work. This will substantiate the definition of phenotypic subsets, allow for meaningful comparison between analogous subsets in different tissues as well as definition of tissue-specific adaptations (e.g. chemokine receptors specific to one tissue or another among otherwise similar types of B cells). It will also provide many insights into the function of both newly discovered and previously known B cell types; gene expression and phenotype will allow alignment with better-studied analogous murine cell types, strengthening both human and murine lines of work. Again, a wealth of information useful to practically all human immune research will result. Finally, we will take advantage of unique properties of lymphocytes-clonal VDJ rearrangements-and in particular of B cells- somatic hypermutation-to obtain a dynamic picture from an otherwise static analysis. This will be enabled by the exponentially expanding capability of