Single adult human CD34(+)/Lin(-)/CD38(-) progenitors give rise to naturalkiller cells, B-lineage cells, dendritic cells, and myeloid cells

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. P rogenitors were cultured in limiting dilutions with interleukin-7 (IL-7), f lt3 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 f rom 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 o f IL-3 at culture initiation was essential for multilineage differentiation from single cells. Single and double lineage progeny were frequently detec ted, but more importantly, 2% of single cells could give rise to at least t hree lineages (NK cells, B-lineage cells, and DC or myeloid cells) providin g direct evidence that NK and B-lineage differentiation derive from a commo n lymphomyeloid hematopoietic progenitor under the same conditions. This st udy provides new insights into the role of the microenvironment niche, whic h governs the earliest events in lymphoid development. (C) 1999 by The Amer ican Society of Hematology.