B cell population structure in mouse and man

小鼠和人的 B 细胞群结构

基本信息

批准号：
9753465
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
项目类别：
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/9753465
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 Diagnostic Environment Experimental Models Exposure to Expression Profiling Flow Cytometry Genetic Transcription Gut Mucosa Health Hematological Disease Human Humoral Immunities Imagery Immune Immune response Immunofluorescence Immunologic 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 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

项目摘要

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.

抽象的： B细胞负责维持体液免疫。但是，鼠的综合空间地图缺乏人体组织室跨组织室的人类B细胞子集。这些研究的障碍缺乏用于全面分析来自许多不同组织的大量细胞的方法，还可以使用稀有的人类标本。在这里，我们使用高级计算和公正的方法组织B细胞子集及其在小鼠和人中的信号传导特性。我们将测试B细胞的假设子集组成可以通过组织部位预测，并且不同组织部位的长寿命PC具有反映其独特的微环境的独特监管计划。在AIM 1中，我们将确定鼠类和人类B谱系子集的种群结构在整个人体中使用公正的方法。在AIM 2中，我们将建立组织特定的调节程序和鼠的克隆关系 PC（LLPC）来自两个不同的微环境，BM与肠道。这项研究的结果将揭示 B子集的全球人口结构负责体液免疫，并提供有关B细胞如何的见解控制感染在区域和系统上。