Slow receptor acquisition by NK cells regenerated in vivo from transplanted fetal liver or adult bone marrow stem cells

Abstract

Objective Adult mouse natural killer (NK) cells express two families of MHC class I–specific receptors, namely Ly49 and CD94/NKG2, whereas fetal and neonatal NK cells express only CD94/NKG2. After birth, Ly49 + NK cells slowly increase and CD94/NKG2 + NK cells decrease. The aim of this study was to determine whether murine NK cells develop differently from transplants of fetal liver and adult marrow stem cells and whether the adult marrow microenvironment is critical for NK receptor maturation. Materials and methods Enriched populations of stem cells were transplanted into adult mice, and the kinetics of NK receptor acquisition was examined. NK cells from osteopetrotic Csf1 op/Csf1 op mice, in which hematopoiesis within the marrow is severely limited, were also analyzed. Results NK cells regenerated from both fetal and adult stem cells initially resembled neonatal NK cells in their slow acquisition of Ly49 over several weeks, although the adult stem cell–derived NK cells matured approximately 10 days sooner. NK cells from adult Csf1 op/Csf1 op mice expressed normal levels of Ly49. Conclusion Maturation of the NK receptor repertoire is a slow process regardless of their stem cell origin or reduced marrow space caused by osteopetrosis.