VDJRearrangement

VDJ rearrangement, also called V(D)J recombination, is the process by which the variable regions of immunoglobulin (antibody) and T-cell receptor (TCR) genes are assembled during lymphocyte development. This somatic DNA recombination creates diverse antigen receptors from a limited set of gene segments, enabling recognition of a vast array of pathogens.

The rearrangement is carried out by the RAG1 and RAG2 endonuclease complex, which recognizes recombination signal sequences flanking V, D, and J gene segments. The 12/23 rule governs which segments can join, ensuring proper assembly (for example, heavy-chain D and J join first, then a V segment joins to form VDJ).

The DNA double-strand breaks are repaired by the non-homologous end joining pathway, yielding a coding joint. Junctional diversity is created by exonuclease trimming and by adding non-templated (N) and palindromic (P) nucleotides, contributing to repertoire diversity beyond the combinatorial possibilities of segment choice.

In B cells, rearrangement of the heavy chain (V-D-J) occurs in developing B cells in the bone marrow, followed by light-chain rearrangement (V-J). In T cells, beta chain rearranges first (V-D-J), then alpha chain (V-J) rearranges in the thymus.

Allelic exclusion ensures that most lymphocytes express a single type of receptor; receptor editing can rescue cells if a rearrangement is nonfunctional.

After successful rearrangement, transcription and translation produce membrane-bound receptors, and further diversification occurs via somatic hypermutation and class-switch recombination later in B cells, though these processes are separate from VDJ rearrangement.

Clinical relevance: defects in RAG genes or other components of the rearrangement machinery cause immunodeficiency disorders such as SCID or Omenn syndrome; improper rearrangements can contribute to lymphoid malignancies through chromosomal translocations.

VDJ rearrangement is therefore central to adaptive immunity, providing the initial receptor diversity that enables antigen-specific responses.