VDJ

VDJ refers to the somatic recombination of variable (V), diversity (D), and joining (J) gene segments that generates the diverse antigen receptor genes of B and T lymphocytes. This mechanism creates the variable regions of immunoglobulin chains in B cells and T-cell receptor chains in T cells, enabling recognition of a wide array of antigens.

In B cells, the heavy chain locus rearranges V, D, and J segments to form a functional variable region, while the light chain loci rearrange V and J segments (kappa and lambda). In T cells, the beta chain uses V, D, and J segments; the alpha chain uses V and J segments. Gamma and delta T-cell receptor loci have their own rearrangement patterns, with delta rearranging from a separate locus that can involve V, D, and J segments.

The rearrangement is initiated by the RAG1 and RAG2 recombinases, which cut DNA at recombination signal sequences flanking the V, D, and J segments. The resulting breaks are repaired by the non-homologous end joining pathway, producing a coding joint that encodes the variable region and a signal joint that is usually excised. Junctional diversity adds further variation through imprecise joining, P-nucleotide additions, and N-nucleotide additions by terminal deoxynucleotidyl transferase (TdT).

VDJ recombination occurs during lymphocyte development in primary lymphoid organs (bone marrow for B cells and thymus for T cells). It is tightly regulated, including allelic exclusion to ensure each lymphocyte expresses a single antigen receptor.

Defects in VDJ recombination or RAG genes can cause immunodeficiencies such as severe combined immunodeficiency and related syndromes, underscoring its critical role in adaptive immunity.