Two recently discovered genes, the recombination activating genes 1 an
d 2 (RAG-1 and RAG-2), are necessary to perform variable (V), diversit
y (D), and joining (J) recombination. They synergistically activate VD
J recombination to generate immunocompetent lymphocytes. Disruption of
either gene results in a maturation arrest at a very early B and T ce
ll progenitor stage. Expression and downregulation of RAG's are closel
y associated with interleukin 7, sIgM and TCR-CD3 complex, respectivel
y. Assessment of RAG mRNA expression is a valuable marker in identifyi
ng the genotypic maturation status of leukemias and lymphomas. Persist
ent RAG expression in otherwise mature lymphoid proliferations may exp
lain puzzling biological and clinical observations such as multiple re
arrangements in lymphomas with a mature phenotype. Lack of RAG express
ion in Hodgkin's disease with abundant Reed-Sternberg cells is consist
ent with a mature phenotype of the latter. Availability of a anti-RAG-
1 monoclonal antibody in the near future will facilitate RAG analysis
of lymphomas.