Natural Killer Cell Development and Maturation Revisited: Possible Implications of a Novel Distinct Lin−CD34+DNAM-1brightCXCR4+ Cell Progenitor

Federica Bozzano, Francesco Marras, Andrea De Maria

Since the first description of natural killer (NK) cells, the view on their role in innate immunity has evolved considerably. In addition to first-line defense against transformed and pathogen-infected autologous cells, NK cells contribute to modulate adaptive immune responses and in some cases acquire specialized functions, including exhausted, adaptive, and decidual NK cells. NK cells derive from CD34(+) progenitors, in vivo and in vitro; however, it is unclear whether the high phenotype diversity in vivo may be generated from these precursors alone. The recent characterization of a novel CD34(+)DNAM-1(bright)CXCR4(+) precursor giving rise to apparently licensed and functional maturing NK cells may suggest the possibility for a higher than expected common lymphocyte precursor diversity and a consequently higher peripheral NK cell phenotype variability. Here, we review the evidences on NK cell central and peripheral development from CD34(+) precursors and propose a possible updated reading frame based on the characterization of CD34(+)DNAM-1(bright)CXCR4(+) cell progenies, which favors the possibility of concurrent NK cell maturation from different CD34(+) precursors.