Department of Microbiology and Immunology
College of Physicians and Surgeons, Columbia University, USA
Dr. Uttiya Basu did his doctoral training in molecular biology with Dr. Umadas Maitra at the Albert Einstein College of Medicine, New York. Thereafter he did his post-doctoral training in Immunology as aIrvington Institute Fellow with Dr. Frederick Alt at Harvard School of Medicine, Boston. At present he is a assistant professor in immunology at the Department of Microbiology and Immunology, Columbia University, New York. He is a fellow of the Leukemia and Lymphoma Society of America, Irma Hirschl Foundation and Leukemia Research Foundation.
Dr. Uttiya Basu research interests include antibodies are polypeptide complexes produced by B-lymphocytes of the immune system that identify and neutralize pathogens, such as bacteria and viruses. Antibodies are comprised of immunoglobulin (Ig) heavy (IgH) and light (IgL) chain polypeptides. Each polypeptide has an N-terminal variable region that facilitates its binding to antigen, whereas the C-terminal constant region of the IgH chain is necessary for downstream effector functions. There are three DNA alteration events that allow mammalian B lymphocytes to achieve enormous antibody diversification: V(D)J recombination, class switch recombination and somatic hypermutation. Developing B cells, in the bone marrow, undergo V(D)J recombination to assemble exons encoding the IgH and IgL variable (V) regions upstream of the corresponding constant region exons. Thereafter, the newly generated B cells migrate to secondary lymphoid organs where they encounter antigens, and are stimulated to further undergo two additional Ig gene alterations, class switch recombination (CSR) and somatic hypermutation (SHM). CSR is a B cell-specific DNA rearrangement reaction that replaces the initial Ig heavy chain constant region gene exon Cmu with other downstream constant region exons so that secondary isotypes (IgG, IgA etc) with different effector functions are generated. SHM, on the other hand, introduces point mutations into V genes at a very high rate, ultimately leading to increased antibody affinity. Although CSR and SHM are distinct processes, they both require transcription through the relevant Ig loci, and activity of the enzyme activation induced cytidine deaminase (AID). Human patients with inactivating mutations in the AID gene suffer from severe immunodeficiency leading to Hyper-IgM syndrome (HIGM2), whereas hyperactivity of AID leads to various B and T cell malignancies.