Location and cellular stages of natural killer cell development

• Hematopoietic progenitor cells follow discrete stages to differentiate into mature NK cells.
• NK cells develop in bone marrow as well as in some extramedullary sites, such as lymph nodes, thymus, liver, and uterus.
• NK cell development is controlled by both extracellular and intracellular factors.

The identification of distinct tissue-specific natural killer (NK) cell populations that apparently mature from local precursor populations has brought new insight into the diversity and developmental regulation of this important lymphoid subset. NK cells provide a necessary link between the early (innate) and late (adaptive) immune responses to infection. Gaining a better understanding of the processes that govern NK cell development should allow us to harness better NK cell functions in multiple clinical settings, as well as to gain further insight into how these cells undergo malignant transformation. In this review, we summarize recent advances in understanding sites and cellular stages of NK cell development in humans and mice.