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: 8172998
• 负责人: Bapi Pahar
• 金额: $ 6.18万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172998
• 关键词: Antibody Formation; Antigens; Axillary lymph node group; B Cell Proliferation; B-Lymphocyte Subsets; B-Lymphocytes; Bone Marrow; Bromodeoxyuridine; Bronchoalveolar Lavage; Computer Retrieval of Information on Scientific Projects Database; Data; Disease Outcome; Flow Cytometry; Frequencies; Funding; Grant; Immunoglobulin G; Immunoglobulins; Immunophenotyping; Infection; Institution; Lamina Propria; Lymphocyte; Lymphoid Tissue; Macaca; Macaca mulatta; Memory B-Lymphocyte; Plasma; Population; Production; Research; Research Personnel; Resources; Role; SIV; Source; Spleen; T-Lymphocyte; Tissues; Tonsil; United States National Institutes of Health; Viral Load result; jejunum; lymph nodes; nonhuman primate; peripheral blood; receptor expression; 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. In this study we have performed an extensive analysis of B cells obtained from peripheral blood, axillary lymph node, bronchoalveolar lavage, bone marrow, spleen, tonsil and lamina propria lymphocytes (LPL) of the jejunum from normal and SIV infected rhesus macaques by polychromatic flow cytometry. We have further characterized memory B cell population and their role in inducing antibody responses. The distribution, frequency, and immunophenotype in regards to activation, proliferation and maturation receptor expression of different B cell subsets were examined from macaques infected with SIVMAC251. Furthermore, we examined and compared levels of turnover of different B cell subsets in lymphoid tissues to correlate their proliferation with plasma viral load and disease outcome. 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, LPL 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。 在这项研究中，我们通过多色流对从正常和感染 SIV 的恒河猴的外周血、腋窝淋巴结、支气管肺泡灌洗液、骨髓、脾脏、扁桃体和空肠固有层淋巴细胞 (LPL) 中获得的 B 细胞进行了广泛的分析细胞计数术。我们进一步表征了记忆 B 细胞群及其在诱导抗体反应中的作用。对感染 SIVMAC251 的猕猴检查不同 B 细胞亚群的激活、增殖和成熟受体表达的分布、频率和免疫表型。此外，我们检查并比较了淋巴组织中不同 B 细胞亚群的周转水平，以将其增殖与血浆病毒载量和疾病结果相关联。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中 CD21+CD27+B 细胞增殖增加，随后是脾脏、空肠 LPL、淋巴结和外周血。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。