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.

项目概要/摘要 过敏性免疫反应导致多种疾病的发病机制。 IgE 同种型抗体 在过敏性免疫反应的启动中发挥关键作用。在过敏个体中，IgE 的产生是通过 对环境或食物抗原的特异性。通常，这种 IgE 的产生是为了响应重复的 抗原暴露。然而，从根本上讲，人们对细胞动力学知之甚少。 抗体回忆反应中重复接触抗原后 IgE 的产生。为了攻克技术 由于研究产生 IgE 的细胞存在困难，我们和其他小组开发了方法，包括 生成荧光 IgE 报告小鼠，通过流式细胞术直接检测 IgE B 细胞和浆细胞 和显微镜。迄今为止，这些方法论的进步为不同的领域提供了重要的新见解。 初级阶段表达 IgE 的 B 细胞和浆细胞与其他同种型相比的特征 免疫反应。我们现在建议应用这种方法来直接研究表达 IgE 的 B 细胞和 浆细胞再次暴露于抗原。本研究的总体目标是表征 促进或抑制 IgE 产生的抗体回忆反应的特征。本研究的具体目标 目的是：1) 确定抗体回忆反应中 IgE 浆细胞的细胞起源，以及 2) 阐明如何 记忆 B 细胞和生发中心 B 细胞影响二次免疫的 IgE 反应。这些研究 将为了解抗体回忆反应期间 IgE 反应如何调节提供重要的新见解，这 将增加我们对过敏性疾病中 IgE 产生如何发生的了解。