Post genomic structural and functional aspects of antibody in heath and disease

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For host defence, disease prevention and therapy, knowledge of the immune system and its regulation in health and disease is of fundamental importance. Towards this goal, our research is focused on 'antibody genetics and autoimmunity'. We made an original discovery of unique functional IgM antibodies in cattle, the largest known to exist in a species. This offers opportunity to develop novel antibody engineering strategies for prevention of those diseases where conventional therapies fail, e.g., cancer, autoimmune diseases and viral infections. My proposed research aims at defining 'structure-function' relationships of these novel types of antibodies and, also to develop a vaccine against bovine leukemia virus. These studies also involve understanding the development of the neonatal immune system aimed at strengthening the host defence of newborns against infections. Other studies are focused on the origin of autoantibodies that cause systemic autoimmune disease, such as Lupus and arthritis. We have observed that pathogenic autoantibodies originate from the impaired development of the antibody repertoire at newborn stage. The role of B-cell selection in generating systemic autoimmune disease is not well understood. The proposed studies are aimed at identifying the anatomical location where white blood cells (B-cells) producing pathogenic autoantibodies, especially of the IgM type, originate so that these could be targeted for elimination by therapeutic intervention in patients afflicted with autoimmune disease. The IgM autoantibody type is studied since these appear first and initiate autoimmune disease.