V(D)J recombination

How is it regulated? V(D)J recombination is regulated in a tissue-specific, lineage-specific and stage-specific manner. The V, D and J segments are recombined in an ordered sequence (D–J rearrangements before V–DJ). As you might expect, the process is partly regulated via the expression of RAG1 and RAG2, but it is also mediated by the differential accessibility of particular antigen receptor loci to the RAG recombinase (the RAG1–RAG2 complex). ‘Allelic exclusion’ is an additional level of regulation whereby only one allele is recombined if a productive antigen receptor is made. What’s special about the RAG genes? RAG1 and RAG2 could be remnants of an ancient transposon that inserted into the germline of a vertebrate ancestor. In vitro, the RAG proteins can excise a fragment of DNA containing RSSs and integrate it randomly into a target DNA molecule via a mechanism similar to retroviral integration and transposition. Inappropriate transposase activity of RAG1 and RAG2 could cause the DNA translocations associated with certain lymphatic tumors.