IMPORTANCE OF ANTIGEN SPECIFIC IGA RESPONSES IN CONTROLLING SIV/SHIV INFECTION

抗原特异性 IGA 反应在控制 SIV/SHIV 感染中的重要性

• 批准号: 7958680
• 负责人: Bapi Pahar
• 金额: $ 6.04万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7958680
• 关键词: Antibody Formation; Antigens; B Cell Proliferation; B-Lymphocytes; Bromodeoxyuridine; Complement 3d Receptors; Computer Retrieval of Information on Scientific Projects Database; Data; Funding; Grant; HIV; Humoral Immunities; Immunoglobulin G; Immunoglobulins; In Vitro; Individual; Infection; Institution; Lamina Propria; Lead; Macaca; Macaca mulatta; Memory B-Lymphocyte; Mitogens; Pathogenesis; Plasma Cells; Primates; Production; Reporting; Research; Research Personnel; Resources; Role; SIV; Satellite Viruses; Source; Spleen; Structure of germinal center of lymph node; T-Lymphocyte; Tissues; Tonsil; United States National Institutes of Health; exhaustion; jejunum; lymph nodes; peripheral blood; premature; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Memory B cells are generated in germinal centers and contribute to humoral immunity by rapidly differentiating into plasma cells. Recent report on HIV pathogenesis suggests that the virus associated premature exhaustion of tissue-like memory B cells may lead to poor antibody responses in HIV infected individuals. Here we have demonstrated the expression of CD21 and CD27 molecules on B cells isolated from different tissues as well as their rate of proliferation in both normal healthy uninfected and SIVMAC251 infected rhesus macaques. We have also studied the role of single positive CD27+ B cells isolated from peripheral blood compared to their double positive (CD21+CD27+) B cell counterparts in inducing immunoglobulin production after in vitro mitogen stimulation. Our findings demonstrate that CD27 expression on B cells varies in different tissues and that double positive CD21+CD27+ B cells are capable of producing increased IgG compared to single positive CD27+ B cells after 3 days of stimulation. Furthermore, their immunoglobulin production is not dependent on T cell help suggestive of memory B cells. We have also observed an increased proliferation of CD21+CD27+ B cells in the tonsil followed by spleen, jejunum lamina propria, lymph node and peripheral blood from normal uninfected rhesus macaques after single BrdU inoculation. Following SIV infection the proliferation of CD21+CD27+ memory B cells dramatically decreased in all the tissues as compared to normal uninfected macaques. A significant reduction of CD21+CD27+ memory B cells was evident in tonsil (p0.004). These data suggest that SIV infection may contribute defective antibody response by inhibiting memory B cell proliferation in tissues.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 记忆B细胞是在生发中心产生的，并通过迅速分化为浆细胞而导致体液免疫。关于HIV发病机理的最新报告表明，与组织样记忆B细胞相关的病毒过早耗尽可能导致HIV感染个体的抗体反应不良。在这里，我们证明了从不同组织分离的B细胞上CD21和CD27分子的表达，以及它们在正常健康的未感染和SIVMAC251感染的恒河猴的正常健康中的增殖率。我们还研究了与双阳性（CD21+CD27+）B细胞对应物中从外周血分离的单个阳性CD27+B细胞在体外促丝裂原后诱导免疫球蛋白产生中的作用。我们的发现表明，与单个阳性CD27+ B细胞相比，在刺激3天后，与单个阳性阳性CD27+ B细胞相比，双胞胎阳性CD21+ CD27+ B细胞在不同组织中的CD27表达在不同的组织中有所不同。此外，它们的免疫球蛋白的产生不取决于T细胞有助于暗示记忆B细胞。我们还观察到扁桃体中CD21+ CD27+ B细胞的增殖增加，随后是脾脏，脾脏，空肠lamina lamina propria，淋巴结和外周血，来自正常未感染的恒河猕猴，单次BRDU接种后。 SIV感染后，与正常未感染的猕猴相比，所有组织中CD21+ CD27+记忆B细胞的增殖均大幅下降。在扁桃体中，CD21+ CD27+记忆B细胞的显着降低（P0.004）是明显的。这些数据表明，SIV感染可能通过抑制组织中的记忆B细胞增殖来造成缺陷的抗体反应。