Development of B cell memory in allergic asthma

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Project Summary/Abstract Allergic asthma is a chronic inflammatory disease of the lungs without cure. Repetitive allergen exposure in the airway leads to the generation of pathogenic immune memory and the excessive production of allergen specific IgE antibodies that mediate inflammation, airway constriction and respiratory distress in patients with allergic asthma. Memory B cells are a key component of immune memory. The phenotypic and functional heterogeneity of MBCs affords their differential antibody responses as well as impact their trafficking, tissue retention and ability to disseminate systemically. In a mouse model of allergic lung inflammation, we have observed stable lung- localized MBCs and evidence for the generation of pathogenic antibody responses in sensitized lungs. We hypothesize that after local antigen sensitization, the lung acquires immune functions reminiscent of those in secondary lymphoid tissues, capable of maintaining long-lived memory B cells as well as generating new MBCs that can recirculate and disseminate in other tissues to mediate systemic allergic inflammation. In this study, we will 1) probe the development of memory B cells (MBCs) in allergic lungs including in-depth characterization of the critical MBC subset that contributes to allergen specific IgE response, and 2) how these MBCs disseminate systemically. We will also 3) explore strategies to intercept the systemic dissemination of pathogenic MBCs to halt the progression of allergic inflammation. These studies will advance our fundamental understanding of memory B cells as well as help devise new therapeutic strategies for allergic asthma.