Figure 4.
A 3-stage model of NK development. The cytoplasmic CD3+ nuclear TdT+ bipotent T/NK-cell precursor may develop into either immature T cells under the actions of E2A and IL-2, or immature NK cells under the actions of ID2 and IL-15. Lineage commitment is fully established when immature T cells complete TCR gene rearrangement, or, as our data support, immature NK cells express CD94 1A transcripts. The model shows where the cytokines and transcription factors are critical, but does not exclude their possible roles at other developmental stages. For example, the assignment of ID2 before IL-15 is based on previous data23 and a recent review.41 According to this model, the loss of ID2 in NK-LBLs is due to abnormal differentiation. Whether the expression of IL-15Rα or, equivalently, the role of IL-15, might precede that of ID2 in the development of normal NK cells, requires further investigation.