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.

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