B CELL MEMORY AND ORIGINAL ANTIGENIC SIN

B 细胞记忆和原罪抗原

• 批准号: 8357483
• 负责人: JOSHY JACOB
• 金额: $ 4.12万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357483
• 关键词: Activated Lymphocyte; Antigens; B-Lymphocytes; Data Analyses; Funding; Grant; Human; Immune response; Immunology; Influenza; Life; Lymphocyte; Memory; Memory B-Lymphocyte; Mus; National Center for Research Resources; Primates; Principal Investigator; Proliferating; Research; Research Infrastructure; Resources; Sanguisorba; Scheme; Source; T-Lymphocyte; United States National Institutes of Health; Vaccinated; Vaccine Research; cohort; cost; influenza virus vaccine; influenzavirus; pandemic influenza; response; theories

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. Burnet's clonal selection theory, the reigning paradigm in immunology, dictates that antigen selects specific lymphocytes from a large repertoire of T and B cells and induces them to selectively proliferate. These activated lymphocytes facilitate rapid antigen clearance and, upon neutralization of the antigenic threat, they persist in the host as memory lymphocytes for a lifetime. Later in life, encounter with the same antigen induces massive proliferation of these memory lymphocytes and rapid clearance of the antigen. While this scheme holds true for most immune responses, the phenomenon of "original antigenic sin", first described in humans vaccinated against influenza virus, stands out as a paradox to Burnet's rules of B cell engagement (Fazekas de St and Webster, 1966a). This project seeks to understand B cell memory as it relates to original antigenic sin responses to both strains and subtypes of influenza virus. Since original antigenic sin can drastically dampen immune responses to newer strains of influenza it is critical to understand the fundamentals of this phenomenon as this has tremendous implications for influenza vaccine research particularly with pandemic influenza looming on the horizon. In order to investigate the mechanism of original antigenic sin we have immunized cohorts of mice with inactivated influenza viruses, and we continue to collect and analyze the data concerning their immune responses.

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。 伯内特的克隆选择理论是免疫学的主导范式，它规定抗原从大量 T 和 B 细胞中选择特定的淋巴细胞，并诱导它们选择性增殖。这些活化的淋巴细胞促进快速抗原清除，并且在中和抗原威胁后，它们作为记忆淋巴细胞在宿主中持续存在一生。在以后的生活中，遇到相同的抗原会引起这些记忆淋巴细胞的大量增殖和抗原的快速清除。虽然这一方案适用于大多数免疫反应，但首次在接种流感病毒疫苗的人类中描述的“原始抗原原罪”现象与 Burnet 的 B 细胞参与规则相矛盾（Fazekas de St 和 Webster，1966a）。该项目旨在了解 B 细胞记忆，因为它与对流感病毒株和亚型的原始抗原反应有关。由于原始抗原罪可以极大地抑制对新流感病毒株的免疫反应，因此了解这种现象的基本原理至关重要，因为这对流感疫苗研究具有巨大影响，特别是在大流行性流感即将来临的情况下。为了研究原始抗原原罪的机制，我们用灭活的流感病毒对小鼠进行了免疫接种，并继续收集和分析有关其免疫反应的数据。