Tracing the Evolution of Adaptive Immunity
Dr. Cooper and his colleagues perform comparative studies of lymphocyte development and function with an aim to better understand the cell differentiation defects in individuals with immunodeficiency diseases, lymphoid malignancies, and autoimmune diseases. Highlights of his laboratory’s research include the delineation of separate T- and B-cell lineages, identification of the hematopoietic tissue origin of B-lineage cells, identification of precursor B cells, demonstration that IgM-bearing B lymphocytes give rise to B cells that switch to the production of other Ig isotypes, description of the lymphoid follicle associated epithelial “M” cells in the intestine and their transcytotic function, demonstration that TCR excision circles can be used to identify recent thymic emigrants, and discovery of an alternative adaptive immune system in jawless vertebrates featuring antigen receptors generated by the assembly of leucine-rich-repeat sequences. Current studies focus on the evolution of the adaptive immune system and the development of monoclonal lamprey antibodies for biomedical uses.
A search for the origin of our adaptive immune system has revealed that the jawed vertebrates and jawless vertebrates (lampreys and hagfish) use different strategies for generating large repertoires of lymphocyte receptors for antigens. Whereas lymphocytes in jawed vertebrates undergo RAG-mediated recombinatorial assembly of immunoglobulin V, D, and J gene segments to generate diverse T-cell receptor (TCR) and B-cell receptor (BCR) repertoires, lymphocytes in jawless vertebrates employ leucine-rich repeat (LRR) gene segments as templates to complete the assembly of variable lymphocyte receptor (VLR) genes. Three VLR loci (VLRA, VLRB and VLRC) undergo independent assembly during the differentiation of three distinct lymphocyte lineages. The VLRA-bearing and VLRC-bearing lymphocytes have genetic programs and phenotypic characteristics that resemble those of certain T cells of jawed vertebrates, whereas the VLRB-bearing cells resemble B cells. Dr. Cooper’s lab concludes that the basic genetic programs for the T and B cell lineages were already present in a common vertebrate ancestor more than 500 million years ago, prior to the convergent evolution of different types of anticipatory receptors.
The page was last updated on Thursday, March 26, 2015 - 5:58pm