NK cell development and maturation in humans and mice. Early stages of natural killer (NK) cell development are identical between humans and mice with the hematopoietic stem cell that progresses to the common lymphoid progenitor (CLP) with c-KIT, FLT3, and IL-7R expression. The CLP then differentiates into the NK progenitor (NKP) that is marked by expression of IL-2Rβ (CD122). As the NK cell continues to develop, differences arise in the markers between humans and mice, but analogous receptors are expressed at each stage by the NK cells. In the immature NK cell stage that develops from the NKP, CD2 is expressed in both humans and mice with the addition of the NK-cell receptor protein 1 molecule (NK1.1 in many strains of mice or CD161 in humans). The next stage is the immature lytic NK cell, where human NK cells start to express CD56 and mouse NK cells express DX5. This is followed by expression of CD94 in both humans and mice. The final, mature lytic stage of NK cells is determined by the expression of receptors that are capable of binding to MHC-I and related molecules: the Ly49s in mice and the killer cell immunoglobulin-like receptors in humans. The NK cells can now leave the bone marrow and head out into the periphery in their mature state.⁴⁰