A Human CD34(+) Subset Resides in Lymph Nodes and Differentiates into CD56brightNatural Killer Cells

SummaryIn humans, T cells differentiate in thymus and B cells develop in bone marrow (BM), but the natural killer (NK) precursor cell(s) and site(s) of NK development are unclear. The CD56bright NK subset predominates in lymph nodes (LN) and produces abundant cytokines compared to the cytolytic CD56dim NK cell that predominates in blood. Here, we identify a novel CD34dimCD45RA(+) hematopoietic precursor cell (HPC) that is integrin α4β7bright. CD34dimCD45RA(+)β7bright HPCs constitute <1% of BM CD34(+) HPCs and ∼6% of blood CD34(+) HPCs, but >95% of LN CD34(+) HPCs. They reside in the parafollicular T cell regions of LN with CD56bright NK cells, and when stimulated by IL-15, IL-2, or activated LN T cells, they become CD56bright NK cells. The data identify a new NK precursor and support a model of human NK development in which BM-derived CD34dimCD45RA(+)β7bright HPCs reside in LN where endogenous cytokines drive their differentiation to CD56bright NK cells in vivo