PAS · Persistence of allergic sensitization

Allergic disorders are dramatically increasing in the western world over the past several years. Allergies are inappropriate immune responses directed against harmless environmental antigens. Upon primary allergen encounter B cells are induced to differentiate into IgE producing plasma cells. Mast cells and basophils are then sensitized by binding of allergen-specific IgE molecules to the high-affinity IgE receptor on the cell surface. A second allergen exposure causes cross-linking of IgE molecules on mast cells and basophils which results in degranulation of pro-inflammatory mediators. Allergen-specific IgE can be detected many months after the sensitization phase despite the fact that IgE has a very short half-life. This suggests that small amounts of allergen-specific IgE are constantly secreted by long-lived IgE producing plasma cells. The development, turnover and fate of IgE producing cells in vivo are largely unknown. Therefore, we propose to study these important issues by using genetically modified mouse strains and cutting edge technology. We will use IgE-FLAG-GFP reporter mice to trace IgE-producing cells in vivo by fluorescence microscopy and 2-photon live imaging. The reporter mice will allow us to isolate IgE-producing cells so that we can determine their gene expression profile. Furthermore, we will determine the turnover and lifespan of IgE producing cells in vivo by BrdU incorporation. Finally, we will generate an IgE-Cre knock-in mouse to specifically delete conditional alleles in IgE-producing cells. Taken together, these important experiments will help us to better understand the biology of IgE-producing cells and may result in development of novel therapeutic strategies.