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. 1986 Apr 1;163(4):872–883. doi: 10.1084/jem.163.4.872

Differentiation of dendritic cells in cultures of rat bone marrow cells

PMCID: PMC2188067  PMID: 3512761

Abstract

Although dendritic cells (DC) originate from bone marrow, they were not observed in fresh preparations of bone marrow cells (BMC). Likewise, accessory activity was barely measurable in a sensitive assay for this potent function of DC. However, both DC and accessory activity developed when BMC were cultured for 5 d. Based on fractionation before culture, nearly all of the accessory activity could be attributed to only 5% of the total BMC recovered in a low-density (LD) fraction. The LD-DC precursors differed from mature DC in a number of important respects. Removal of Ia+ cells from the LD fraction by panning did not decrease the production of DC when the nonadherent cells were cultured. Thus, the cell from which the DC is derived does not express or minimally expresses Ia antigens, in contrast to the strongly Ia+ DC that is produced in bone marrow cultures. Irradiation of LD cells before culture prevented the development of DC. When irradiation was delayed by daily intervals, progressive increases in the number of DC resulted, up to the fifth day. These findings, together with preliminary autoradiographic data, indicate that cell division has occurred, in contrast to the DC, which does not divide. We conclude that bone marrow-derived DC arise in culture from the division of LD, Ia- precursors.

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Selected References

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  1. Austyn J. M., Steinman R. M., Weinstein D. E., Granelli-Piperno A., Palladino M. A. Dendritic cells initiate a two-stage mechanism for T lymphocyte proliferation. J Exp Med. 1983 Apr 1;157(4):1101–1115. doi: 10.1084/jem.157.4.1101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barclay A. N. Different reticular elements in rat lymphoid tissue identified by localization of Ia, Thy-1 and MRC OX 2 antigens. Immunology. 1981 Dec;44(4):727–736. [PMC free article] [PubMed] [Google Scholar]
  3. Beyer C. F., Bowers W. E. Lymphocyte transformation induced by chemical modification of membrane components. I. Characteristics of the direct and indirect restimulation responses of rat lymph node cells to periodate. J Immunol. 1977 Dec;119(6):2120–2128. [PubMed] [Google Scholar]
  4. Bowers W. E., Berkowitz M. R. Removal of rat dendritic cells from single cell suspensions by passage through columns of Sephadex G-10. J Immunol Methods. 1984 Nov 30;74(2):317–325. doi: 10.1016/0022-1759(84)90299-0. [DOI] [PubMed] [Google Scholar]
  5. Bowers W. E., Goodell E. M. Dendritic cells: historical perspective and role in oxidative mitogenesis. Immunobiology. 1984 Dec;168(3-5):274–284. doi: 10.1016/S0171-2985(84)80116-3. [DOI] [PubMed] [Google Scholar]
  6. Castagnola C., Visser J., Boersma W., van Bekkum D. W. Purification of rat pluripotent hemopoietic stem cells. Stem Cells. 1982;1(4-5):250–260. [PubMed] [Google Scholar]
  7. Drexhage H. A., Mullink H., de Groot J., Clarke J., Balfour B. M. A study of cells present in peripheral lymph of pigs with special reference to a type of cell resembling the Langerhans cell. Cell Tissue Res. 1979 Nov;202(3):407–430. doi: 10.1007/BF00220434. [DOI] [PubMed] [Google Scholar]
  8. Fossum S. Characterization of Ia+ non-lymphoid cells in peripheral lymph from congenitally athymic nude rats. Scand J Immunol. 1984 Jan;19(1):49–61. doi: 10.1111/j.1365-3083.1984.tb00899.x. [DOI] [PubMed] [Google Scholar]
  9. Fossum S., Ford W. L. The organization of cell populations within lymph nodes: their origin, life history and functional relationships. Histopathology. 1985 May;9(5):469–499. doi: 10.1111/j.1365-2559.1985.tb02830.x. [DOI] [PubMed] [Google Scholar]
  10. Fossum S., Rolstad B., Ford W. L. Thymus independence, kinetics and phagocytic ability of interdigitating cells. Immunobiology. 1984 Dec;168(3-5):403–413. doi: 10.1016/S0171-2985(84)80126-6. [DOI] [PubMed] [Google Scholar]
  11. Frelinger J. G., Hood L., Hill S., Frelinger J. A. Mouse epidermal Ia molecules have a bone marrow origin. Nature. 1979 Nov 15;282(5736):321–323. doi: 10.1038/282321a0. [DOI] [PubMed] [Google Scholar]
  12. Hart D. N., Fabre J. W. Demonstration and characterization of Ia-positive dendritic cells in the interstitial connective tissues of rat heart and other tissues, but not brain. J Exp Med. 1981 Aug 1;154(2):347–361. doi: 10.1084/jem.154.2.347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Inaba K., Steinman R. M., Van Voorhis W. C., Muramatsu S. Dendritic cells are critical accessory cells for thymus-dependent antibody responses in mouse and in man. Proc Natl Acad Sci U S A. 1983 Oct;80(19):6041–6045. doi: 10.1073/pnas.80.19.6041. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Klinkert W. E., LaBadie J. H., Bowers W. E. Accessory and stimulating properties of dendritic cells and macrophages isolated from various rat tissues. J Exp Med. 1982 Jul 1;156(1):1–19. doi: 10.1084/jem.156.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Klinkert W. E., LaBadie J. H., O'Brien J. P., Beyer C. F., Bowers W. E. Rat dendritic cells function as accessory cells and control the production of a soluble factor required for mitogenic responses of T lymphocytes. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5414–5418. doi: 10.1073/pnas.77.9.5414. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Klinkert W. E. Rat bone marrow precursors develop into dendritic accessory cells under the influence of a conditioned medium. Immunobiology. 1984 Dec;168(3-5):414–424. doi: 10.1016/S0171-2985(84)80127-8. [DOI] [PubMed] [Google Scholar]
  17. Knight S. C. Veiled cells--"dendritic cells" of the peripheral lymph. Immunobiology. 1984 Dec;168(3-5):349–361. doi: 10.1016/S0171-2985(84)80122-9. [DOI] [PubMed] [Google Scholar]
  18. Mayrhofer G., Pugh C. W., Barclay A. N. The distribution, ontogeny and origin in the rat of Ia-positive cells with dendritic morphology and of Ia antigen in epithelia, with special reference to the intestine. Eur J Immunol. 1983 Feb;13(2):112–122. doi: 10.1002/eji.1830130206. [DOI] [PubMed] [Google Scholar]
  19. Phillips M. L., Wettstein P. J., O'Brien R. L., Parker J. W., Frelinger J. A. Characterization of responding cells in oxidative mitogen stimulation. I. Ia+ cells and Ly-1+2+ cells are required for the proliferative response. J Immunol. 1980 Jun;124(6):2693–2699. [PubMed] [Google Scholar]
  20. Pugh C. W., MacPherson G. G., Steer H. W. Characterization of nonlymphoid cells derived from rat peripheral lymph. J Exp Med. 1983 Jun 1;157(6):1758–1779. doi: 10.1084/jem.157.6.1758. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Silberberg-Sinakin I., Thorbecke G. J., Baer R. L., Rosenthal S. A., Berezowsky V. Antigen-bearing langerhans cells in skin, dermal lymphatics and in lymph nodes. Cell Immunol. 1976 Aug;25(2):137–151. doi: 10.1016/0008-8749(76)90105-2. [DOI] [PubMed] [Google Scholar]
  22. Spry C. J., Pflug A. J., Janossy G., Humphrey J. H. Large mononuclear (veiled) cells like 'Ia-like' membrane antigens in human afferent lympn. Clin Exp Immunol. 1980 Mar;39(3):750–755. [PMC free article] [PubMed] [Google Scholar]
  23. Steinman R. M., Cohn Z. A. Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution. J Exp Med. 1973 May 1;137(5):1142–1162. doi: 10.1084/jem.137.5.1142. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Steinman R. M., Kaplan G., Witmer M. D., Cohn Z. A. Identification of a novel cell type in peripheral lymphoid organs of mice. V. Purification of spleen dendritic cells, new surface markers, and maintenance in vitro. J Exp Med. 1979 Jan 1;149(1):1–16. doi: 10.1084/jem.149.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Steinman R. M., Witmer M. D. Lymphoid dendritic cells are potent stimulators of the primary mixed leukocyte reaction in mice. Proc Natl Acad Sci U S A. 1978 Oct;75(10):5132–5136. doi: 10.1073/pnas.75.10.5132. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Stingl G., Katz S. I., Clement L., Green I., Shevach E. M. Immunologic functions of Ia-bearing epidermal Langerhans cells. J Immunol. 1978 Nov;121(5):2005–2013. [PubMed] [Google Scholar]
  27. Streilein J. W., Bergstresser P. R. Langerhans cells: antigen presenting cells of the epidermis. Immunobiology. 1984 Dec;168(3-5):285–300. doi: 10.1016/S0171-2985(84)80117-5. [DOI] [PubMed] [Google Scholar]
  28. Tew J. G., Thorbecke G. J., Steinman R. M. Dendritic cells in the immune response: characteristics and recommended nomenclature (A report from the Reticuloendothelial Society Committee on Nomenclature). J Reticuloendothel Soc. 1982 May;31(5):371–380. [PubMed] [Google Scholar]
  29. Till J. E., McCulloch E. A. Hemopoietic stem cell differentiation. Biochim Biophys Acta. 1980 Nov 26;605(4):431–459. doi: 10.1016/0304-419x(80)90009-8. [DOI] [PubMed] [Google Scholar]
  30. Van Voorhis W. C., Hair L. S., Steinman R. M., Kaplan G. Human dendritic cells. Enrichment and characterization from peripheral blood. J Exp Med. 1982 Apr 1;155(4):1172–1187. doi: 10.1084/jem.155.4.1172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Veerman A. J. On the interdigitating cells in the thymus-dependent area of the rat spleen: a relation between the mononuclear phagocyte system and T-lymphocytes. Cell Tissue Res. 1974 Apr 11;148(2):247–257. doi: 10.1007/BF00224586. [DOI] [PubMed] [Google Scholar]
  32. Wong T. W., Klinkert W. E., Bowers W. E. Immunological properties of thymus cell subpopulations: rat thymic dendritic cells are potent accessory cells and stimulators in a mixed leukocyte culture. Immunobiology. 1982 Feb;160(5):413–423. doi: 10.1016/S0171-2985(82)80005-3. [DOI] [PubMed] [Google Scholar]
  33. Wysocki L. J., Sato V. L. "Panning" for lymphocytes: a method for cell selection. Proc Natl Acad Sci U S A. 1978 Jun;75(6):2844–2848. doi: 10.1073/pnas.75.6.2844. [DOI] [PMC free article] [PubMed] [Google Scholar]

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