Cellular Origin of IgE Recall Responses

项目总结/摘要 过敏性免疫反应有助于许多疾病的发病机制。IgE同种型抗体 在过敏性免疫应答的起始中起关键作用。在过敏性个体中，IgE是由 对环境或食物抗原的特异性。通常，这种IgE的产生是响应于重复的免疫应答而发生的。 抗原暴露然而，在基本水平上，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的细胞时遇到了困难，我们和其他小组开发了方法，包括 产生荧光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，这些方法上的进步为我们提供了重要的新见解， 与其他同种型相比，在原发性免疫缺陷综合征中表达IgE的B细胞和浆细胞的特征 免疫反应。我们现在建议应用这种方法直接研究表达IgE的B细胞， 浆细胞在再次暴露于抗原的情况下。本研究的总体目标是描述 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）确定抗体回忆应答中IgE浆细胞的细胞起源，2）阐明 记忆B细胞和生发中心B细胞影响对二次免疫的IgE应答。这些研究 将提供关键的新的见解，IgE反应是如何调节抗体回忆反应， 将增加我们对过敏性疾病中IgE产生的理解。

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.