Characterization of a novel bipotent hematopoietic progenitor population in normal and osteopetrotic mice

Several reports indicate that osteoclasts and B-lymphocytes share a common progenitor. This study focuses on the characterization of this bipotent progenitor from the bone marrow of the osteopetrotic oc/oc mouse, where the bipotent progenitor population is amplified, and of normal mice.

Osteoclasts have a myelomonocytic origin, but they can also arise in vitro from pro-B-cells, suggesting that a subset of normal pro-B-cells is uncommitted and may reorient into the myeloid lineage representing a B-lymphoid/osteoclastic progenitor. The aim of this study was to characterize this progenitor population.

The osteopetrotic oc/oc mouse was used as a choice model because it displays an increased number of both osteoclasts and pro-B-cells in the bone marrow. Our results have been confirmed in normal littermates. Bone marrow cells from these animals were analyzed by flow cytometry. After sorting, the cells were cultured under different conditions to assess their differentiation capacity.

Pro-B-cells from oc/oc and normal mice include an unusual biphenotypic population expressing markers from the B-lymphoid (CD19, CD43, CD5) and the myeloid (F4/80) lineages. This population also expresses progenitor markers (CD34 and Flt3) and is uncommitted. After sorting from the oc/oc bone marrow, this population is able to differentiate in vitro into osteoclast-like cells in the presence of RANKL and macrophage colony-stimulating factor (M-CSF), into dendritic-like cells in the presence of granulocyte/macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-4, and TNFalpha, and into immature B-cells when seeded onto ST2 cells in the presence of IL-7.

Our results show the existence of a novel bipotent biphenotypic hematopoietic progenitor population present in the bone marrow that has retained the capacity to differentiate into myeloid and B-lymphoid cells.