In vertebrates, the adoptive immune system recognizes and responds to many foreign antigens by way of the antigen-specific immunoglobulin/B-cell receptor (Ig/BCR) or T-cell receptor (TCR) molecules expressed on the cell surface of B and T lymphocytes, respectively. The Ig receptor of B cells binds to soluble antigens, whereas the TCR recognizes peptide antigens presented by human leukocyte antigen (HLA) molecules.

BCR and TCR genes are generated through the lymphocyte-specific V(D)J recombination process. Lymphocyte-specific and ubiquitous DNA repair proteins involved in this process have been highly conserved throughout evolution. Naturally occurring mutations in the two lymphocyte-specific V(D)J recombination machinery components, recombinase-activating gene 1 and 2 (RAG1 and RAG2), lead to primary immunodeficiencies, indicating the crucial need for the integrity of V(D)J recombination for lymphoid development. A complete RAG1 or RAG2 deficiency causes severe combined immunodeficiency without B and T cells (B⁻T⁻ severe combined immunodeficiencies [SCID]). In contrast, partial RAG defects result in Omenn's syndrome, an immune deficiency with autoreactive manifestations caused by a residual, oligoclonal lymphocyte repertoire.