Production and differentiation of NK linkage cells in bone marrow

The production of natural killer (NK) cells from their bone marrow progenitors is a multistep developmental process requiring interaction of hemopoietic NK lineage cells, stromal cells and growth factors. In this review, recent studies on the generation of NK cells provide the basis for a model of NK cell production. The development of NK cells is suggested to be similar to that of B cells, the other major lymphocyte population produced in the bone marrow. This scheme, for which substantial data already exist and which is testable vis-à-vis other points, can be summarized as follows: large, proliferating progenitor NK cells (pro-NK) give rise, under the influence of stromal cells and/or growth factors to less rapidly proliferating NK precursor cells (pre-NK) which exhibit some but not all of the phenotypic and morphologic characteristics of NK cells. Pre-NK cells divided and differentiate into phenotypically recognizable primary NK cells in the bone marrow. Primary NK cells are not in cell cycle, have low but measurable lytic activity, and express the phenotype of resting NK cells. They exit the bone marrow to populate peripheral sites where they undergo further maturation, become activated by such agents as interferon and may undergo a new cycle of proliferation in response to viral infections or other stimuli.