Cellular Origin of IgE Recall Responses

IgE 回忆反应的细胞起源

• 批准号: 10728196
• 负责人: Christopher David Caballero Allen
• 金额: $ 23.94万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-08 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10728196
• 关键词: Affect; Affinity; Allergic; Allergic Disease; Antibodies; Antigens; B-Cell Antigen Receptor; B-Lymphocyte Subsets; B-Lymphocytes; Biology; Cells; Characteristics; Data; Detection; Disease; Exposure to; Flow Cytometry; Generations; Goals; Human; Hypersensitivity; IgE; IgG1; Immune response; Immunization; Immunoglobulin Class Switching; Immunoglobulin Switch Recombination; Individual; Lead; Memory B-Lymphocyte; Methodology; Microscopy; Mus; Pathogenesis; Plasma Cells; Play; Predisposition; Procedures; Production; Regulation; Reporter; Role; Sampling; Secondary Immunization; Secondary to; Signal Transduction; Specificity; Stable Populations; Stains; Structure of germinal center of lymph node; Vaccination; cytokine; food antigen; improved; insight; interleukin-21; novel strategies; pathogen; response

Project Summary/Abstract Allergic immune responses contribute to the pathogenesis of numerous diseases. Antibodies of the IgE isotype play a critical role in the initiation of allergic immune responses. In allergic individuals, IgE is produced with specificity for environmental or food antigens. Typically, this IgE production occurs in response to repetitive antigen exposure. However, at a fundamental level, remarkably little is known about the cellular dynamics of IgE production upon repetitive antigen exposure in antibody recall responses. In order to overcome technical difficulties in studying the cells that produce IgE, we and other groups developed methodology, including the generation of fluorescent IgE reporter mice, to directly detect IgE B cells and plasma cells by flow cytometry and microscopy. These methodological advances have thus far provided critical new insights into the distinct characteristics of B cells and plasma cells expressing IgE compared with other isotypes during primary immune responses. We now propose to apply this methodology to directly study IgE-expressing B cells and plasma cells in the context of re-exposure to antigen. The overall objective of this study is to characterize features of antibody recall responses that promote or suppress IgE production. The specific goals of this study are to: 1) determine the cellular origin(s) of IgE plasma cells in antibody recall responses and 2) elucidate how memory B cells and germinal center B cells affect IgE responses to secondary immunization. These studies will provide critical new insights into how IgE responses are regulated during antibody recall responses, which will increase our understanding of how IgE production occurs in allergic disease.

项目摘要/摘要 过敏性免疫反应在许多疾病的发病机制中起作用。免疫球蛋白E亚型抗体 在启动过敏性免疫反应中起关键作用。在过敏的个体中，IgE是由 环境或食物抗原的专一性。通常，这种IgE的产生是对重复的 抗原暴露。然而，在根本层面上，人们对细胞动力学知之甚少。 抗体召回反应中重复抗原暴露产生的免疫球蛋白。为了克服技术上的困难 在研究产生IgE的细胞方面的困难，我们和其他小组开发了方法学，包括 用流式细胞术直接检测IgE B细胞和浆细胞的方法 和显微镜。到目前为止，这些方法学上的进步为我们提供了对不同的 原发期表达IgE的B细胞和浆细胞与其他亚型的比较 免疫反应。我们现在建议将这一方法应用于直接研究表达IgE的B细胞和 在浆细胞再次暴露于抗原的背景下。这项研究的总体目标是 促进或抑制IgE产生的抗体召回反应的特征。这项研究的具体目标 目的是：1)确定抗体召回反应中免疫球蛋白E浆细胞的细胞来源(S)；2)阐明 记忆B细胞和生发中心B细胞影响二次免疫的IgE应答。这些研究 将为在抗体召回反应过程中如何调节IgE反应提供关键的新见解，这 将增加我们对过敏性疾病中IgE产生的理解。