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Blood, Vol. 93 No. 1 (January 1), 1999:
pp. 96-106
Single Adult Human
CD34+/Lin /CD38 Progenitors
Give Rise to Natural Killer Cells, B-Lineage Cells,
Dendritic Cells, and Myeloid Cells
Jeffrey S. Miller,
Valarie McCullar,
Michael Punzel,
Ihor R. Lemischka, and
Kateri A. Moore
From the Department of Medicine, University of Minnesota Cancer
Center, Minneapolis, MN; and the Department of Molecular Biology,
Princeton University, Princeton, NJ.
Marrow stromal cultures support adult
CD34+/Lin /HLA-DR or
CD34+/Lin/CD38 cell
differentiation into natural killer (NK) or myeloid cells, but unlike
committed lymphoid progenitors
(CD34+/Lin/CD45RA+/CD10+),
no B cells are generated. We tested whether different microenvironments could establish a developmental link between the NK and B-cell lineages. Progenitors were cultured in limiting dilutions with interleukin-7 (IL-7), flt3 ligand (FL), c-kit ligand (KL), IL-3, IL-2,
and AFT024, a murine fetal liver line, which supports culture of
transplantable murine stem cells. NK cells,
CD10+/CD19+ B-lineage cells and dendritic
cells (DC) developed from the same starting population and IL-7, FL,
and KL were required in this process. Single cell deposition of 3,872 CD34+/Lin/CD38 cells onto
AFT024 with IL-7, FL, KL, IL-2, and IL-3 showed that a one time
addition of IL-3 at culture initiation was essential for multilineage
differentiation from single cells. Single and double lineage progeny
were frequently detected, but more importantly, 2% of single cells
could give rise to at least three lineages (NK cells, B-lineage cells,
and DC or myeloid cells) providing direct evidence that NK and
B-lineage differentiation derive from a common lymphomyeloid
hematopoietic progenitor under the same conditions. This study provides
new insights into the role of the microenvironment niche, which governs
the earliest events in lymphoid development.
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