DOUBLE POSITIVE CD21+CD27+ B CELLS ARE IN MUCOSAL AND PERIPHERAL TISSUES

粘膜和外周组织中存在双阳性 CD21 CD27 B 细胞

• 批准号: 8358167
• 负责人: Bapi Pahar
• 金额: $ 5.78万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8358167
• 关键词: Antibody Formation; B-Lymphocytes; Bromodeoxyuridine; Cells; Chronic; Complement 3d Receptors; Defect; Frequencies; Functional disorder; Funding; Grant; HIV; Immune system; Immunophenotyping; Infection; Lymphoid; Lymphoid Tissue; MS4A1 gene; Macaca mulatta; Mediating; Memory B-Lymphocyte; Mucous Membrane; National Center for Research Resources; Pathogenesis; Patients; Peripheral; Play; Population; Primates; Principal Investigator; Proliferating; Research; Research Infrastructure; Resources; Role; SIV; Sorting - Cell Movement; Source; Surface; T-Lymphocyte; Tissues; Tonsil; United States National Institutes of Health; Viral Load result; Virus Diseases; base; cost; in vivo; peripheral blood; polyclonal antibody

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Several B-cell defects arise in HIV infected patients, particularly in patients with chronic infection and high viral load. Loss of memory B cells (CD27+ B cells) in peripheral blood and lymphoid tissues is one of the major B cell dysfunction in HIV and simian immunodeficiency virus (SIV) infection. Despite several studies, definitive identification of memory B cells based on CD27 surface expression has not been described. Similarly, the rates of cell turnover in different B cell subpopulation from lymphoid and mucosal tissues have not been well documented. In this study, we demonstrate the presence of memory B cell populations and define their distribution, frequency and immunophenotype with regards to activation, proliferation, maturation, and antibody production in normal rhesus macaques from different lymphoid tissues. Thirteen healthy, uninfected rhesus macaques were selected for this study. CD20+ B cells were isolated from peripheral blood and sorted based on CD27 and CD21 surface markers to define memory B cell population. All the B cell subpopulation was further characterized phenotypically and their cell turnover rates were evaluated in vivo following bromodeoxyuridine (BrdU) inoculation. Double positive (DP) CD21+CD27+ B cells in both peripheral and lymphoid tissues are memory B cells, able to produce antibody by polyclonal activation, and without T cell help. Peripheral and Lymphoid DP CD21+CD27+ B cells were also able to become activated and proliferate at higher rates than other B cell subpopulations. Increased turnover of tonsillar memory B cells were identified compared to other tissues examined. We suggest that this DP memory B cells play a major role in the immune system and their function and proliferation might have an important role in HIV/SIV mediated B cell dysregulation and pathogenesis.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 HIV 感染患者中会出现多种 B 细胞缺陷，尤其是慢性感染和高病毒载量的患者。外周血和淋巴组织中记忆 B 细胞（CD27+ B 细胞）的丧失是 HIV 和猿猴免疫缺陷病毒 (SIV) 感染的主要 B 细胞功能障碍之一。尽管进行了多项研究，但尚未描述基于 CD27 表面表达的记忆 B 细胞的明确鉴定。同样，来自淋巴和粘膜组织的不同 B 细胞亚群的细胞更新率尚未得到充分记录。在这项研究中，我们证明了记忆 B 细胞群的存在，并定义了它们在来自不同淋巴组织的正常恒河猴中的激活、增殖、成熟和抗体产生方面的分布、频率和免疫表型。本研究选择了 13 只健康、未感染的恒河猴。从外周血中分离出 CD20+ B 细胞，并根据 CD27 和 CD21 表面标记物进行分类，以确定记忆 B 细胞群。对所有 B 细胞亚群进行了进一步的表型表征，并在接种溴脱氧尿苷 (BrdU) 后在体内评估了它们的细胞更新率。外周组织和淋巴组织中的双阳性 (DP) CD21+CD27+ B 细胞是记忆 B 细胞，能够通过多克隆激活产生抗体，无需 T 细胞帮助。外周和淋巴 DP CD21+CD27+ B 细胞也能够比其他 B 细胞亚群以更高的速度被激活和增殖。与检查的其他组织相比，扁桃体记忆 B 细胞的周转率有所增加。我们认为这种 DP 记忆 B 细胞在免疫系统中发挥着重要作用，其功能和增殖可能在 HIV/SIV 介导的 B 细胞失调和发病机制中发挥重要作用。