Project 170857

The immune system is critical to human health. In order to develop vaccines and treatments for diseases where the immune system malfunctions (such as immunodeficiency, autoimmunity, allergy and asthma), we need to better understand the fundamental mechanisms governing immune responses. Our research deals with the arm of the immune system responsible for producing antibodies, which are specialized proteins that bind to microorganisms (the antigen) and target them for destruction by the immune system. Besides this protective role, antibodies can have destructive pathogenic roles, for example anti-DNA antibodies in Lupus, and allergen-binding IgE antibodies in atopic disease. Antibodies are secreted into the blood and mucosal surface by cells called B lymphocytes. B lymphocytes are controlled by receptor proteins on their cell surface which allow them to sense the presence of antigens, tissue damage and other activated cells. These receptors also provide signals telling the cells where to go within the body during an immune response. Cell surface receptors deliver signals to the interior of the cell through another set of proteins known as signal transduction proteins. Our research aims to define the specific molecular signaling pathways that regulate the activities of B lymphocytes during normal and abnormal immune responses. In this grant proposal we will investigate the roles of molecules in the PI 3-kinase signaling pathway in controlling selection of B cells producing protective antibodies or allergen-binding IgE antibodies.

using mouse genetic models to study B lymphocyte signaling pathways and germinal center responses