Granulocytes, Macrophages, and Dendritic Cells Arise from a Common Major Histocompatibility Complex Class II-Negative Progenitor in Mouse Bone Marrow

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 90; no. 7; pp. 3038 - 3042
• Main Authors: Inaba, Kayo, Inaba, Muneo, Deguchi, Masashi, Hagi, Katsuhiko, Yasumizu, Ryoji, Ikehara, Susumu, Muramatsu, Shigru, Steinman, Ralph M.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01-04-1993; National Acad Sciences; National Academy of Sciences
• Subjects: Animals; Antigens; B lymphocytes; Bacteria; Biological and medical sciences; Bone marrow; Bone Marrow - immunology; Bone Marrow Cells; Cell Adhesion; Cell Differentiation; Cells, Cultured; Cellular biology; Crosses, Genetic; Cultured cells; Dendritic cells; Dendritic Cells - cytology; Dendritic Cells - drug effects; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology; Granulocytes; Granulocytes - cytology; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - drug effects; Hematopoietic Stem Cells - immunology; Histocompatibility Antigens Class II - analysis; Immunity (Disease); Immunobiology; Macrophages; Macrophages - cytology; Mice; Mice, Inbred Strains; Monoclonal antibodies; Myeloid cells: ontogeny, maturation, markers, receptors; Phagocytes; Phenotype; Polynuclears; Rodents; T lymphocytes; Vacuoles - ultrastructure; Dendritic cell; Major histocompatibility system; Cytokine; Rodentia; Class II histocompatibility antigen; Granulocyte; In vitro; Precursor; Vertebrata; Phenotype; Regulation(control); Mammalia; Mouse; Development; Bone marrow; Granulocyte macrophage colony stimulating factor; Macrophage
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.90.7.3038

The developmental origin of dendritic cells, a specialized system of major histocompatibility complex (MHC) class II-rich antigen-presenting cells for T-cell immunity and tolerance, is not well characterized. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is known to stimulate dendritic cells, including growth and development from MHC class II-negative precursors in suspension cultures of mouse bone marrow. Here we studied colony formation in semi-solid methylcellulose cultures, a classical bioassay system in which GM-CSF induces the formation of mixed granulocyte-macrophage colonies. When colonies were induced from MHC class II-negative precursors, a small subset (1-2%) of typical dendritic cells developed alongside macrophages and granulocytes. The dendritic cells were distinguished by their cytologic features, high levels of MHC class II products, and distinct intracellular granule antigens. By using differential adherence to plastic, enriched populations of the various myeloid cell types were isolated from colonies. Only the dendritic cells stimulated a primary T-cell immune response, the mixed leukocyte reaction, and the potency was comparable to typical dendritic cells isolated from spleen. Macrophages from mixed or pure colonies were inactive as stimulator cells. Therefore, three distinct pathways of myeloid development-granulocytes, macrophages, and dendritic cells-can develop from a common MHC class II-negative progenitor under the aegis of GM-CSF.