Allergic diseases, such as asthma, affect tens of millions of people and are increasing in prevalence, particularly in children. An underlying feature of many of these allergic responses is the production of IgE antibodies specific for allergens, which are typically harmless substances such as pollen and cat dander. When these allergens are inhaled, they are bound by specific IgE antibodies that are captured on the surface of mast cells and basophils through the high-affinity IgE receptor Fc-epsilon-RI, thereby triggering these cells to degranulate and release pro-inflammatory mediators that in turn recruit other inflammatory cells.
Despite the significant role of IgE in allergic disease, the cellular biology of IgE is poorly understood. Indeed, little is known about the generation and localization of B cells that produce IgE, and the orchestration of inflammatory responses by IgE has not been well-characterized in vivo.
We are applying sophisticated imaging, flow cytometry, mouse genetics, and other techniques to uncover novel paradigms regulating IgE and downstream inflammatory responses. Our laboratory has recently generated fluorescent IgE reporter mice allowing us to identify and track rare IgE-producing B cells in vivo. We are using two-photon microscopy to directly visualize cellular interactions in situ during allergic immune responses. Our major research goals are to:
- Identify the in vivo mechanisms leading to the production of IgE antibodies in allergic responses versus the suppression of IgE antibodies in healthy individuals.
- Determine the in vivo functions of basophils that have bound IgE antibodies specific for allergens.
- Characterize the interactions among inflammatory cells in the lung in asthma and define the features of the microenvironments in which these interactions occur.
Yang Z., Sullivan B.M., Allen C.D.C. (2012). Fluorescent in vivo detection reveals that IgE+ B cells are restrained by an intrinsic cell fate predisposition. Immunity, 36(5), 857-872.
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Allen C.D.C., Okada T., Tang H.L., Cyster J.G. (2007). Imaging of germinal center selection events during affinity maturation. Science, 315(5811), 528-531.
Allen C.D.C., Ansel K.M., Low C., Lesley R., Tamamura H., Fujii N. Cyster J.G. (2004). Germinal center dark and light zone organization is mediated by CXCR4 and CXCR5. Nature Immunology, 5(9), 943-952.