The role of AID in the Immune response

B-lymphocytes derive from haematopoietic stem cells in the bone marrow and home to secondary lymphoid organs as mature cells. Upon encounter with invading pathogenic determinants, they are activated and begin to proliferate. In a complex interplay with other white blood cells, this activation process leads to the formation of a germinal centre reaction that culminates in the transformation of the mature B cell into a terminally differentiated plasma cell. The only function of the plasma cell is to produce antibodies, which capture pathogenic determinants for their subsequent neutralization. Most intriguingly, the germinal centre reaction, if misguided, is responsible for a couple of severe immune-pathologic disorders like lymphomas, immunodeficiencies and autoimmune diseases. In this project we want to study the role of the Activation Induced cytidine Deaminase (AID) in the germinal centre reaction. Recently, the Activation Induced cytidine Deaminase (AID) gene has been identified in the mouse and its expression is strictly restricted to germinal centre B cells and B cells activated in vitro. Mice and humans deficient in AID have a severely perturbed germinal centre reaction. It was suggested that AID needs the binding of cofactors to selectively recruit AID for distinct functions during the germinal centre reaction. However, these cofactors still remain to be identified. The goal of the project is the characterization of human AID protein, the identification of its interaction partners and finally, the functional analysis of AID mutants and mutants of AID-interacting proteins using the chicken cell line DT40. These experiments will be important for a better understanding of the germinal centre reaction and to design effective treatments for germinal centre associated diseases.