Cellular Origin of IgE Recall Responses

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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.