Demonstration of the origin of human mast cells from CD34+ bone marrow progenitor cells.
It has been established that murine mast cells are derived from a pluripotent bone marrow stem cell. In humans, the corresponding pluripotent cell is included in the CD34+ bone marrow population. To determine whether human mast cells arise from CD34+ human progenitor cells, enriched CD34+ cells were cultured over agarose surfaces (interphase cultures) or cocultured with mouse 3T3 fibroblasts in the presence of recombinant human (rh) IL-3. The presence of both mast cells and basophils was determined using a variety of histochemical and immunohistologic techniques, including immunogold labeling for IgE receptors and mast cell tryptase. Mast cells and basophils continued to appear in cultures when T cell, B cell, macrophage, and eosinophil committed progenitor cells were removed, but were not seen in cultures from which CD34+ cells were removed. CD34+ cells layered over agarose in the presence of rhIL-3 were shown to give rise to cultures that contained mast cells (1 to 5%) and basophils (25 to 40%). Cultures supplemented with rhIL-4 showed no additional increase in mast cells or basophils. CD34+ cells cocultured with 3T3 fibroblasts in the presence of rhIL-3 gave rise to mast cells within the fibroblast monolayer, which by 6 wk comprised up to 46% of the monolayer. CD34-cells on 3T3 fibroblasts gave rise to few mast cells (2% of the monolayer). Mast cell granules from interphase cultures contained homogeneous electron-dense material. In contrast, mast cells within 3T3 monolayers at 6 wk contained a variety of granule morphologies, including scroll, mixed, reticular, dense core, or homogeneous patterns. We conclude that both human mast cells and basophils arise from CD34+ human progenitor cells.
Kirshenbaum
A S
AS
Mast Cell Physiology Section National Institute of Allergy and Infectious Diseases National Institutes of Health, Bethesda, MD 20892.
Kessler
S W
SW
Goff
J P
JP
Metcalfe
D D
DD
D015703:Antigens, CD / Q000032:analysis*; D018952:Antigens, CD34; D000943:Antigens, Differentiation / Q000032:analysis*; D001402:B-Lymphocytes / Q000166:cytology; D001491:Basophils / Q000166:cytology; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000276:immunology; D004804:Eosinophils / Q000166:cytology; D005347:Fibroblasts / Q000502:physiology; D006801:Humans; D008212:Lymphocyte Depletion; D008264:Macrophages / Q000166:cytology; D008407:Mast Cells / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology* / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology
D015703:Antigens, CD; D018952:Antigens, CD34; D000943:Antigens, Differentiation