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 过敏免疫反应有助于多种疾病的发病机理。 IgE同种型的抗体 在过敏免疫反应的开始中起关键作用。在过敏的个体中，IgE是由 环境或食物抗原的特异性。通常，这种IgE产生是为了响应重复性而发生 抗原暴露。但是，在基本层面上，人们对细胞动力学知之甚少 抗体回忆反应中重复抗原暴露后的IgE产生。为了克服技术 在研究产生IgE细胞的困难，我们和其他群体开发了方法论，包括 通过流式细胞仪直接检测IgE B细胞和浆细胞的生成荧光IgE记者小鼠直接检测IgE B细胞和浆细胞 和显微镜。到目前为止，这些方法论的进步已经为独特的新见解提供 在原发性期间，与其他同种型相比，B细胞和表达IgE的浆细胞的特征 免疫反应。现在，我们建议将这种方法运用直接研究表达IgE的B细胞和 血浆细胞在重新暴露于抗原的背景下。这项研究的总体目的是表征 抗体回忆反应的特征，可促进或抑制IgE产生。这项研究的具体目标 为：1）确定抗体回忆反应中IgE浆细胞的细胞来源，2）阐明如何 记忆B细胞和生发中心B细胞会影响IgE对继发免疫的反应。这些研究 将提供有关在抗体回忆响应中如何调节IgE反应的关键新见解， 将增加我们对IgE产生在过敏性疾病中的发生的理解。