B CELL RESPONSES TO SHIV

B 细胞对 SHIV 的反应

• 批准号: 6362246
• 负责人: DAVID H MARGOLIN
• 金额: $ 12.12万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-03-01 至 2004-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6362246
• 关键词: AIDS; B lymphocyte; Macaca mulatta; antibody formation; antiviral antibody; biochemical evolution; cell population study; cytotoxic T lymphocyte; disease /disorder model; gene rearrangement; helper T lymphocyte; histology; human immunodeficiency virus 1; immunocytochemistry; immunoglobulin genes; interleukin 10; interleukin 4; interleukin 6; leukocyte activation /transformation; molecular cloning; nucleic acid sequence; simian immunodeficiency virus

Dr. David Margolin graduated magna cum laude from Harvard College, and obtained his medical and doctoral degrees from the University of Pennsylvania. Since completing a neurology residency at the Massachusetts General Hospital (MGH), he has been a postdoctoral fellow in the Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center (BIDMC), supported by a fellowship from the Harvard AIDS Institute. At the same time, he served as coordinator of the HIV Neurology services at MGH where he will become an Instructor in Neurology of the Harvard Medical School. He is committed to a full-time career as a clinical scientist. While serum antibodies to HIV-1 have been intensively studied, important questions remain regarding the clonal generation of HIV-1 specific B lymphocytes. In studies employing the SHIV/macaque model, Dr. Margolin will identify B cells producing HIV-1 specific antibodies in situ and clone the genes encoding their immunoglobulins. Localization of virus- specific B cells will be combined with an analysis of the phenotype and cytokine profile of cells that constitute the B cell microenvironment, providing important insights into cellular mechanisms that generate a humoral immune response to the AIDS virus. Comparison of lymphoid tissues obtained during primary SHIV infection and at later timepoints will provide clues to the molecular evolution of HIV-1-specific antibodies. Combined histopathologic analyses and sequencing of immunoglobulins will elucidate important aspects of AIDS immunopathogenesis, defining the clonal dynamics and pathophysiology of follicular hyperplasia, the differential regulation of antibody responses to Env and Gag proteins, and clonal dominance among virus- specific B cells. Dr. Margolin's research and maturation as an investigator will be facilitated by his association with Dr. Normal Letvin, Chief, Division of Viral Pathogenesis at BIDMC and Dr. Anne B. Young, Chief, Neurology at MGH. Dr. Letvin and Dr. Young are fully committed to Dr. Margolin's development as an independent investigator. A committee of distinguished scientists to oversee Dr. Margolin's progress will include two AIDS researchers and a neuroimmunologist.

David Margolin 博士以优异成绩毕业于哈佛大学， 获得英国大学医学和博士学位 宾夕法尼亚州。自从在医院完成神经内科住院医师实习以来 麻省总医院（MGH），博士后 贝斯以色列女执事医疗中心病毒发病机制科 中心 (BIDMC)，由哈佛艾滋病基金会的奖学金支持 研究所。同时，他还担任艾滋病毒协调员。 他将成为 MGH 神经病学服务的讲师 哈佛医学院神经病学。他致力于全职工作 临床科学家的职业生涯。 虽然 HIV-1 血清抗体已被深入研究，但重要的是 关于 HIV-1 特异性 B 的克隆产生仍然存在问题 淋巴细胞。在采用 SHIV/猕猴模型的研究中，Margolin 博士 将识别原位产生 HIV-1 特异性抗体的 B 细胞， 克隆编码其免疫球蛋白的基因。病毒定位- 特定 B 细胞将与表型分析相结合 构成 B 细胞微环境的细胞的细胞因子谱， 提供对产生细胞机制的重要见解 对艾滋病病毒的体液免疫反应。淋巴比较 原发性 SHIV 感染期间及之后时间点获得的组织 将为HIV-1特异性的分子进化提供线索 抗体。结合组织病理学分析和测序 免疫球蛋白将阐明艾滋病的重要方面 免疫发病机制，定义克隆动力学和病理生理学 卵泡增生，抗体的差异调节 对 Env 和 Gag 蛋白的反应以及病毒之间的克隆优势 特定的 B 细胞。 Margolin 博士作为一名研究者的研究和成熟将 得益于他与部门主管 Normal Letvin 博士的联系 BIDMC 病毒发病机制研究员和神经病学主任 Anne B. Young 博士 在麻省总医院。 Letvin 博士和 Young 博士完全致力于 Margolin 博士的工作 作为一名独立调查员的发展。一个由杰出人士组成的委员会 科学家监督马戈林博士的进展将包括两种艾滋病 研究人员和神经免疫学家。