Affinity maturation of the B-cell repertoire

摘要 流感感染或免疫引起强烈的体液反应，但突变， 在流感病毒血凝素（HA）中积累， 季节性：对今年流感的免疫力并不能可靠地保护明年的病毒。 至关重要的是，疫苗的效力受到每个人的感染和接种史的影响 这种影响是长期的，可以追溯到记忆B细胞的隔间 通过预先暴露于HA抗原。这种影响或克隆印迹的免疫学基础， 是记忆B淋巴细胞对交叉反应性HA抗原产生的克隆优势。 克隆印迹或原始抗原sin（OAS）的例子已经有了很好的描述，但 压印的范围、耐久性和结构限制还没有被系统地研究。 在项目2中，我们将使用一种新的方法进行大规模的单B细胞克隆，以确定如何 并且在其中免疫隔室OAS被“储存”，并且为了定义结构性的OAS， 印迹所需的表位和互补位的相似性。两种类型的记忆B细胞是 负责维持体液免疫记忆的IgM+记忆B细胞（IgM+ Bcl 2） 未经历类别切换和类别切换的（例如，IgG+）BcG;这些小的， 静止淋巴细胞存在于次级淋巴器官中，在那里它们被有效地暴露 抗原。这些种群的种群结构和动态， 流感血凝素（HA）是项目2的重点。

Abstract Influenza infection or immunization elicit robust humoral responses but mutations that accumulate in the influenza virus hemagglutinin (HA) render both types of humoral responses seasonal: immunity against this season's flu does not reliably protect against next year's virus. Crucially, vaccine efficacy is influenced by each individual's history of infection and vaccination and this influence is long-lived and can be traced to the memory B cells compartments elicited by prior exposure to HA antigens. The immunological basis of this influence or clonal imprinting, is clonal dominance by memory B lymphocytes generated to cross-reactive HA antigens. Examples of clonal imprinting or original antigenic sin (OAS) have been well described, but the scope, durability, and structural constraints of imprinting have not been systematically studied. In project 2 we will use a novel method for large scale, single B-cell cloning to determine how and in which immunological compartments OAS is “stored” and to define the structural similarities of epitope and paratope necessary for imprinting. Two types of memory B cells are responsible for the maintenance of humoral immune memory, IgM+ memory B cells (IgM+ Bmem) that have not undergone class-switch and class-switched (e.g., IgG+) Bmem; these small, quiescent lymphocytes reside in secondary lymphoid organs, where they are efficiently exposed to antigens. The population structure and dynamics of these populations following exposure to influenza hemagglutinins (HAs) is the focus of Project 2..