B CELL MEMORY AND ORIGINAL ANTIGENIC SIN

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 伯内特的克隆选择理论是免疫学中的主导范式，它规定抗原从大量的T和B细胞中选择特定的淋巴细胞，并诱导它们选择性地增殖。这些被激活的淋巴细胞有助于快速清除抗原，在中和抗原威胁后，它们作为记忆淋巴细胞在宿主体内持续一生。在生命的后期，遇到相同的抗原会导致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“原始抗原罪”现象与Burnet的B细胞结合规则是矛盾的(Fazekas de St和Webster，1966a)。这个项目试图理解B细胞记忆，因为它与流感病毒株和亚型的原始抗原性SIN反应有关。由于原始抗原性SIN可以极大地抑制对新的流感毒株的免疫反应，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的影响，特别是在大流行流感即将到来的情况下。为了研究原始抗原性SIN的机制，我们用灭活的流感病毒免疫了一组小鼠，并继续收集和分析有关它们的免疫反应的数据。

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.