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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 记忆 B 细胞在生发中心生成，通过快速分化为浆细胞而有助于体液免疫。最近关于 HIV 发病机制的报告表明，与组织样记忆 B 细胞过早耗尽相关的病毒可能会导致 HIV 感染者的抗体反应较差。在这里，我们展示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未感染和 SIVMAC251 感染的恒河猴中的增殖率。我们还研究了从外周血分离的单阳性 CD27+ B 细胞与双阳性 (CD21+CD27+) B 细胞对应物在体外有丝分裂原刺激后诱导免疫球蛋白产生中的作用。我们的研究结果表明，B 细胞上的 CD27 表达在不同组织中存在差异，并且在刺激 3 天后，与单阳性 CD27+ B 细胞相比，双阳性 CD21+CD27+ B 细胞能够产生增加的 IgG。此外，它们的免疫球蛋白产生不依赖于记忆 B 细胞的 T 细胞帮助。我们还观察到，在单次 BrdU 接种后，正常未感染的恒河猴扁桃体中 CD21+CD27+ B 细胞的增殖增加，随后是脾脏、空肠固有层、淋巴结和外周血。 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 细胞的增殖均显着减少。扁桃体中 CD21+CD27+ 记忆 B 细胞明显减少 (p0.004)。这些数据表明，SIV 感染可能通过抑制组织中的记忆 B 细胞增殖来导致抗体反应缺陷。