RAG recombinase expression discriminates the development of natural killer cells

V(D)J recombination initiated by recombination-activating gene (RAG) endonucleases is a crucial process for the generation of diversified antigen receptors of T and B lymphocytes but regarded dispensable for the generation of innate natural killer (NK) lymphocytes that lack clonotypic receptors. However, a fraction of human and murine NK cells derives from RAG-expressing progenitors, which have non-productive rearrangements within their Ig and TCR loci. An impact of V(D)J rearrangements on maturation and function of NK cells has been suggested by mouse and human models. We studied the impact of RAG expression ontogeny on NK cell maturation and function by using RAG-fate mapping reporter permanently labeling NK progenitors and mature NK cells.