The process of V(D) J recombination is initiated and controlled by the enzymatic activity of the cytoplasmic proteins called recombinase which are the products of the activating two genes called RAG1 and RAG2 Both genes are expressed in immature B and T lymphocytes and activated V (D) J rearrangement in Ig and TCR genes, which are directed in cis by (RSSs) Also, they show variable expression in lymphoid malignancy of both B and T cell types that suggest their immaturity in antigenic development including all phenotypic and genotypic stages preceding (SIg) expression and T cell types not only by CD3 – TCR negative T cell types but also by CD3 – TCR positive T cell types. Mutation of the two genes account for a spectrum of combined immune deficiencies in humans.