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。 在这项研究中，我们对B细胞进行了广泛的分析，对从正常和Siv感染的麦卡克斯（Rhesus Macaques）的Jejunum的BORMACY淋巴细胞（LPL）获得的B细胞，支气管淋巴结，支气管肺泡灌洗，骨髓，脾脏，扁桃体和层型淋巴细胞（LPL），这些乳腺杏仁菌的甲基链球菌通过多核酸含量cytorry cytorry cytorry cytorry cytorry。我们进一步表征了记忆B细胞种群及其在诱导抗体反应中的作用。从感染了SIVMAC251的猕猴中检查了不同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细胞亚群的营业额和比较水平，以将其增殖与血浆病毒载量和疾病结局相关。我们的发现表明，与单个阳性阳性CD27+ B细胞相比，在刺激6天后，与单个阳性阳性CD27+ B细胞相比，双重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细胞帮助，暗示了记忆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，空肠的LPL，淋巴结的LPL，淋巴结和外周血在一次BRDU后，来自正常未感染的恒河猴。 SIV感染后，与正常未感染的猕猴相比，在扁桃体（P0.05）中，CD21+ CD27+记忆B细胞显着降低，而CD21+ CD27+记忆B细胞的增殖在淋巴结和脾脏组织中急剧增加。这些数据表明，非人类灵长类动物B细胞子集的功能质量（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有缺陷反应。