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: 8358094
• 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/8358094
• 关键词: Antibody Formation; Antigens; B Cell Proliferation; B-Lymphocyte Subsets; B-Lymphocytes; Bromodeoxyuridine; Complement 3d Receptors; Data; Disease Progression; Funding; Grant; HIV; Humoral Immunities; Immunoglobulin G; Immunoglobulins; In Vitro; Individual; Infection; Lamina Propria; Lead; Macaca; Macaca mulatta; Memory B-Lymphocyte; Mitogens; National Center for Research Resources; Pathogenesis; Plasma Cells; Primates; Principal Investigator; Production; Reporting; Research; Research Infrastructure; Resources; Role; SIV; Source; Spleen; Structure of germinal center of lymph node; T-Lymphocyte; Tissues; Tonsil; United States National Institutes of Health; cost; exhaustion; jejunum; lymph nodes; nonhuman primate; peripheral blood; premature; response; simian human immunodeficiency virus

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. Memory B cells are generated in germinal centers and contribute to humoral immunity by rapidly differentiating into plasma cells. A recent report on HIV pathogenesis suggests that disease progression is associated with premature exhaustion of memory B cells that may lead to poor antibody responses in HIV infected individuals. Here we demonstrate 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 also studied the role of single positive CD27+ B cells isolated from peripheral blood compared to 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 6 days of stimulation. Furthermore, their immunoglobulin production is not dependent on T cell help, suggestive of memory B cells. We also observed increased proliferation of CD21+CD27+ B cells in the tonsil followed by spleen, lamina propria of the jejunum, lymph node and peripheral blood from normal uninfected rhesus macaques after a single BrdU inoculation. Following SIV infection a significant reduction of CD21+CD27+ memory B cells was evident in tonsil (p0.05) compared to normal uninfected macaques whereas, the proliferation of CD21+CD27+ memory B cells dramatically increased in lymph node and spleen tissues. These data demonstrate functional qualities (activation) of nonhuman primate B cell subsets and suggest that SIV infection may induce defective responses in specific tissues, by inhibiting memory B cell proliferation in tissues.

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。 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。最近一份关于 HIV 发病机制的报告表明，疾病进展与记忆 B 细胞过早耗尽有关，这可能导致 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 6 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 T 细胞的帮助，这表明是记忆 B 细胞。我们还观察到，在单次 BrdU 接种后，正常未感染恒河猴的扁桃体、脾脏、空肠固有层、淋巴结和外周血中 CD21+CD27+ B 细胞的增殖增加。与正常未感染的猕猴相比，SIV 感染后，扁桃体中 CD21+CD27+ 记忆 B 细胞明显减少 (p0.05)，而淋巴结和脾组织中 CD21+CD27+ 记忆 B 细胞的增殖急剧增加。这些数据证明了非人灵长类 B 细胞亚群的功能品质（激活），并表明 SIV 感染可能通过抑制组织中的记忆 B 细胞增殖来诱导特定组织中的缺陷反应。