Principal Project

COVID19大流行表明迫切需要了解人类B细胞对紧急情况的反应 病原体及其在评估群体免疫中的应用。我们的实验室已经描述了表型， 人类B细胞反应的不同臂的免疫学和分子特征，特别是原始的 人卵泡外效应器B细胞激活途径的特征及其在不同疾病中的作用 记忆和浆细胞的反应。在此基础上，我们建议审问B细胞的不同手臂 对SARS-CoV-2病毒的反应；识别参与SARS-CoV-2早期、持续和 感染后较晚的反应；并确定它们对建立群体免疫的贡献，至少 部分是通过产生保护性的B细胞记忆来实现的。后者是一个基本特征，它可能是 与血清抗体的持久性分离；因此，除非正式 测试过。我们推测，细胞B细胞记忆的建立和评估其大小的能力 质量将是跟踪人口短期再次感染和季节性暴露风险的关键； 设计能够触发这种保护功能的疫苗；并开发基于SARS-CoV-2B细胞的诊断 测试。这些目标将通过使用SARS-CoV-2感染和康复中的血液样本来实现 目的1.SARS-CoV-2特异性B细胞的特性 多维B细胞流式细胞术对细胞来源的准确判断 抗SARS-CoV-2 B细胞反应的大小和持久性将由抗原特异性完成 流式细胞术，并通过多重抗原分析和B细胞群的单细胞分析进行验证。目标 2.SARS-CoV-2特异性B细胞记忆和群体免疫功能的测定表型特征和 在目标1中建立的抗原特异性流式细胞术检测将应用于感染后的中晚期。 时间点以了解：A)SARS-CoV-2特异性B细胞记忆所在的细胞室 居留；b)其质量、数量和在人口中的分布；c)其出处(无论是#年初 晚期细胞前体)；以及d)其一致性或相反，与血清学反应和 长寿命浆细胞(LLPC)的产生。

The COVID19 pandemic illustrates the urgent need for understanding human B cell responses to emergent pathogens and its application to assessing herd immunity. Our laboratories have described the phenotypic, immunological and molecular features of different arms of human B cell responses and in particular, the original characterization of the human extrafollicular effector B cell activation pathway and its contribution to different memory and plasma cells responses. On that basis, we we propose to interrogate the different arms of the B cell response to the SARS-CoV-2 virus; to identify the B cell compartments that participate in the early, ongoing and late post-infection responses; and to determine their contribution to the establishment of herd immunity, at least in part through the generation of protective B cell memory. The latter is an essential feature that could be uncoupled from the persistence of serum antibodies; and therefore, would go unrecognized unless formally tested. We postulate that the establishment of cellular B cell memory and the ability to evaluate its magnitude and quality will be critical to track the risk of the population to short-term re-infection and seasonal exposure; to design vaccines capable to trigger this protective feature; and to develop SARS-CoV-2 B cell-based diagnostic tests. These goals will be accomplished using blood samples from SARS-CoV-2-infected and convalescent individuals through the following specific aims: Aim 1. Characterization of SARS-CoV-2-specific B cell responses through multidimensional B cell flow cytometry A precise adjudication of the cellular origin, magnitude, and persistence of the anti-SARS-CoV-2 B cell response will be accomplished by antigen-specific flow cytometry and validated by multiplex antigen assays and single cell analysis of the B cell populations. Aim 2. Measurement of SARS-CoV-2-specific B cell memory and herd immunity. Phenotypic features and antigen-specific flow cytometry assays established in aim 1, will be applied to intermediate and late post-infection time points in order to understand: a) the cellular compartments in which SARS-CoV-2-specific B cell memory resides; b) its quality, magnitude and distribution within the population; c) its provenance (whether from early of late cellular precursors); and d) its concordance or conversely, uncoupling from serological responses and the generation of long-lived plasma cells (LLPC).