The Organization and Expression of Lymphocyte Receptor Genes (Immunology part 6)

Since the early twentieth century, when it was first recognized that antibody molecules could specifically identify and bind to a vast array of antigens, immunologists have sought to understand how a limited amount of genetic information could encode such a broad range of specific receptor molecules in lymphocytes of the adaptive immune response. It is now known that B- and T-cell receptor molecules are encoded by families of short gene segments, which are uniquely recombined in different lymphocytes to create the receptor repertoire of the adaptive immune system. Receptors in T and B cells consist of two distinct chains that can be recombined in various ways. Additionally, when two receptor gene segments join, further diversity arises through the nontemplated addition of varying numbers of nucleotides at the junctions between segments. These highly variable sequences at the gene segment junctions form the regions on antigen receptors that interact with antigens, known as the complementarity-determining regions. Due to the random addition and deletion of nucleotides at these junctions, many recombined receptor genes fail to encode functional proteins, resulting in the destruction of nascent B and T cells. Thus, the remarkable receptor diversity characteristic of the adaptive immune system demands significant energy expenditure at the cellular level.The timing of these recombination events is precisely regulated during the development of T and B cells. While the overall process of receptor gene generation is similar in both cell types, subtle variations in the details adapt the receptors to the specific functions of each cell type.