Grant: Project Grant

The immune system plays a major role in protecting humans from bacteria, viruses, and toxins (known as antigens). One of the ways that the immune system accomplishes this is by producing antibodies that bind to and neutralize these antigens. Antibodies are small molecules made by B cells. Each B cell makes only one type of antibody which will bind to only one antigen. By changing the antibody stalk, the properties of the antibody are changed. For example, IgM antibodies can be changed to IgG antibodies which can be used by macrophages to engulf bacteria that are coated by these antibodies, or to IgA antibodies that can be secreted into mucosal tissue and neutralize pathogens in the lung or the gut. Changing the antibody class is accomplished by the class switch recombination process, and the key enzyme that initiates this process is called AID. However, much needs to be learned about this process. In this grant proposal, we plan determine the types of mutations and the enzymes that are required by AID to induce class switch recombination. In addition, since AID has been shown to induce chromosomal translocations that are central to the development of lymphomas, this proposal will also examine the types of mutations and enzymes involved in the development of these cancer-causing events. Hence, the proposed work will allow us to determine how an effective antibody response is generated against pathogens, and will also characterize molecular pathways that play important roles in cancer development. This new information will in turn influence vaccine development or the generation of therapeutic agents that target lymphomas.