V(D)J recombination is the mechanism of somatic recombination that occurs only in developing lymphocytes during the early stages of T and B cell maturation. It results in the highly diverse repertoire of antibodies/immunoglobulins and T cell receptors (TCRs) found in B cells and T cells, respectively. The process is a defining feature of the adaptive immune system. V(D)J recombination in mammals occurs in the primary lymphoid organs (bone marrow for B cells and thymus for T cells) and in a nearly random fashion rearranges variable (V), joining (J), and in some cases, diversity (D) gene segments. The process ultimately results in novel amino acid sequences in the antigen-binding regions of immunoglobulins and TCRs that allow for the recognition of antigens from nearly all pathogens including bacteria, viruses, parasites, and worms as well as "altered self cells" as seen in cancer. The recognition can also be allergic in nature (e.g. to pollen or other allergens) or may match host tissues and lead to autoimmunity. In 1987, Susumu Tonegawa was awarded the Nobel Prize in Physiology or Medicine "for his discovery of the genetic principle for generation of antibody diversity". Background Human antibody molecules (including B cell receptors) are composed of heavy and light chains, each of which contains both constant (C) and variable (V) regions, genetically encoded on three loci: The immunoglobulin heavy locus (IGH@) on chromosome 14, containing the gene segments for the immunoglobulin heavy chain. The immunoglobulin kappa (κ) locus (IGK@) on chromosome 2, containing the gene segments for one type (κ) of immunoglobulin light chain. The immunoglobulin lambda (λ) locus (IGL@) on chromosome 22, containing the gene segments for another type (λ) of immunoglobulin light chain. Each heavy chain or light chain gene contains multiple copies of three different types of gene segments for the variable regions of the antibody proteins. For example, the human immunoglobulin heavy chain region contains 2 Constant (Cμ and Cδ) gene segments and 44 Variable (V) gene segments, plus 27 Diversity (D) gene segments and 6 Joining (J) gene segments. The light chain genes possess either a single (Cκ) or four (Cλ) Constant gene segments with numerous V and J gene segments but do not have D gene segments. DNA rearrangement causes one copy of each type of gene segment to go in any given lymphocyte, generating an enormous antibody repertoire; roughly 3×1011 combinations are possible, although some are removed due to self