Affinity maturation of the B-cell repertoire

摘要 流感感染或免疫可引起强烈的体液反应，但突变 在流感病毒中积聚的血凝素(HA)可引起两种类型的体液反应 季节性：对本季流感的免疫力并不能可靠地预防明年的病毒。 至关重要的是，疫苗效力受每个人的感染史和疫苗接种史的影响 这种影响是长期的，可以追溯到记忆B细胞隔间引发的 通过事先接触透明质酸抗原。这种影响或克隆印记的免疫学基础， 是由记忆B淋巴细胞产生的克隆性显性交叉反应的HA抗原。 克隆印迹或原始抗原性SIN(OAS)的例子已经描述得很好了，但 印迹的范围、耐久性和结构限制尚未得到系统的研究。 在项目2中，我们将使用一种大规模单个B细胞克隆的新方法来确定如何 并在其中存储OAS的免疫学隔间和定义结构 印迹所必需的表位和副表位的相似性。两种类型的记忆B细胞是 负责维持体液免疫记忆、IgM记忆B细胞(IgM Bmem) 没有经历过类别切换和类别切换(例如，免疫球蛋白)BMEM；这些小的， 静止的淋巴细胞驻留在次级淋巴器官中，在那里它们被有效地暴露。 对抗原。暴露于空气中后这些人群的种群结构和动态 流感血凝素(HAS)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..