The diverse antigen receptor repertoires of B and T lymphocytes are generated by somatic rearrangement of Ig and TCR V, D, and J gene segments during lymphocyte development. A basic mechanistic understanding of V(D)J recombination reaction is now at hand. The process is initiated by recombinase proteins recombination activating gene (RAG)-1 and RAG-2, which bind to recombination signal sequences (RSSs) that flank Ig and TCR gene segments, recruit a pair of RSSs into a synaptic complex, and generate double strand breaks (DSBs) between the RSSs and coding segments. The reaction is then completed with the additional participation of DSB repair proteins, which help to process and rejoin the coding and signal end molecules to generate coding joints and signal joints, respectively.
V(D)J recombination at the various Ig and TCR loci is highly regulated during lymphocyte development, with lineage- and...