B cell population structure in mouse and man

小鼠和人的 B 细胞群结构

• 批准号: 10225407
• 负责人: Lisa Borghesi
• 金额: $ 38.67万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-21 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10225407
• 关键词: Antibodies; B-Lymphocyte Subsets; B-Lymphocytes; Blood; Blood Circulation; CXCL12 gene; CXCR4 gene; Cell physiology; Cells; Characteristics; Clinical; Clone Cells; Colon; Computational algorithm; Consensus; Data; Environment; Experimental Models; Exposure to; Expression Profiling; Flow Cytometry; Genetic Transcription; Gut Mucosa; Health; Hematological Disease; Human; Humoral Immunities; Immune; Immune response; Immunofluorescence Immunologic; Immunologic Monitoring; Immunologics; Individual; Infection Control; Intestines; Knowledge; Link; Lymphoid; Maintenance; Maps; Mediator of activation protein; Memory B-Lymphocyte; Metabolic; Metabolism; Methods; Microanatomy; Mucous Membrane; Mus; Normal tissue morphology; Pathway interactions; Phenotype; Phosphoproteins; Plasma Cells; Population; Property; Publishing; Signal Pathway; Signal Transduction; Sister; Site; Specimen; Structure; Surface; Testing; Tissues; Visualization; accurate diagnostics; base; differential expression; dimensional analysis; functional status; genome-wide; high dimensionality; human tissue; ileum; improved; in vivo; insight; jejunum; man; mathematical model; microbial; mouse model; novel; programs; protein expression; stem; tissue resource; transcription factor; virtual

Abstract: B cells are responsible for maintaining humoral immunity. However, a comprehensive spatial map of murine and human B cell subsets across tissue compartments in the body is lacking. A barrier to these studies has been the lack of methods for comprehensive analysis of large numbers of cells from many different tissues and also access to rare human specimens. Here we use advanced computing and unbiased approaches to organize B cell subset and their signaling properties in mouse and man. We will test the hypothesis that B cell subset composition can be predicted by tissue site and that long-lived PCs in different tissues sites have distinct regulatory programs that reflect their unique microenvironments. In Aim 1, we will establish the population structure of murine and human B lineage subsets throughout the body using unbiased approaches. In Aim 2, we will establish the tissue-specific regulatory programs and clonal relationships of murine long-lived PC (LLPC) derived from two distinct microenvironments, BM versus gut. Results from this study will reveal the global population structure of B subsets responsible for humoral immunity and provide insights into how B cells control infections regionally and systemically.

摘要： B细胞负责维持体液免疫。然而，一个全面的空间地图， 并且缺乏跨体内组织区室的人类B细胞亚群。这些研究的障碍是 缺乏对来自许多不同组织的大量细胞进行综合分析的方法， 还能接触到稀有的人类标本在这里，我们使用先进的计算和公正的方法， 组织小鼠和人的B细胞亚群及其信号传导特性。我们将检验B细胞 可以通过组织部位预测亚组组成，且不同组织部位中长寿命PC具有 不同的监管计划，反映其独特的微环境。在目标1中，我们将建立 使用无偏的方法，在整个身体中鼠和人B谱系亚群的群体结构。 目的二是建立小鼠长寿基因的组织特异性调控程序和克隆关系 PC（LLPC）来源于两种不同的微环境，BM与肠道。这项研究的结果将揭示 负责体液免疫的B亚群的总体群体结构，并提供了B细胞如何 控制区域性和系统性感染。