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 器官供体-表征正常人免疫系统中的B细胞区室、亚群和反应， 系统我们将强调组织驻留细胞，包括淋巴组织中的细胞和粘膜中的细胞。 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化技术， 分析以全面确定所有受试者中B谱系细胞的表型、亚群和特征， 上述组织。除了发现新的B细胞亚群--一个主要的终点--这项工作将 提供了人类B细胞的独特图谱，并将极大地有助于相关性和数据的解释， PBL通常是人类受试者的唯一可用样本。第二个目标是用基因来定义 工作第一部分确定的关键人群的表达谱。这将证实 表型子集的定义，允许在不同的相似子集之间进行有意义的比较。 组织以及组织特异性适应的定义（例如，对一种组织特异性的趋化因子受体或 另一种在其它类似类型的B细胞中）。它还将提供许多关于两者功能的见解， 新发现的和先前已知的B细胞类型;基因表达和表型将允许比对 与更好地研究的类似小鼠细胞类型相结合，加强了人类和小鼠的工作。我再次重申， 将产生对几乎所有人类免疫研究有用的大量信息。最后，我们将 淋巴细胞-克隆VDJ保留-特别是B细胞-的独特性质的优势 体细胞超变-从静态分析中获得动态图像。这将启用 通过指数增长的能力，

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