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.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 在HIV感染的患者中，特别是在慢性感染和高病毒载量的患者中，出现几种B细胞缺陷。外周血和淋巴组织中记忆B细胞（CD 27 + B细胞）的丧失是HIV和猴免疫缺陷病毒（SIV）感染中的主要B细胞功能障碍之一。尽管进行了几项研究，但尚未描述基于CD 27表面表达的记忆B细胞的明确鉴定。同样，淋巴组织和粘膜组织中不同B细胞亚群的细胞更新率也没有得到很好的记录。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CD 20 + B细胞，并基于CD 27和CD 21表面标志物进行分选以定义记忆B细胞群。所有的B细胞亚群进一步表征表型和他们的细胞更新率进行了评估，在体内后溴脱氧尿苷（BrdU）接种。外周和淋巴组织中的双阳性（DP）CD 21 + CD 27 + B细胞是记忆B细胞，能够通过多克隆活化产生抗体，而无需T细胞帮助。外周和类血小板DP CD 21 + CD 27 + B细胞也能够以比其他B细胞亚群更高的速率活化和增殖。扁桃体记忆B细胞的周转率高于其他组织。我们认为，DP记忆B细胞在免疫系统中发挥重要作用，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。