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A Hodgkin’s Disease Cell Line, KM-H2, Shows Biphenotypic Features of Dendritic Cells and B Cells

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Abstract

The origin of Reed-Sternberg (RS) cells, the neoplastic cells of Hodgkin’s disease, has long remained controversial. Dendritic cells (DCs) are highly specialized antigen-presenting cells that have the unique capacity to prime naive T cells, and they may be progenitors of RS cells in a population of Hodgkin’s disease cells. In this study, the KM-H2 cell line, previously established from a patient with Hodgkin’s disease of mixed cellularity, was reevaluated for its cellular derivation, particularly in terms of DCs. KM-H2 cells were demonstrated to carry the newly proposed DC-associated molecules fascin, CD83, and DEC-205, as well as costimulatory molecules such as CD40, CD80, and CD86. In addition, KM-H2 cells were shown to be able to potently stimulate peripheral blood T cells and to have the strong endocytotic activity of fluorescein isothiocyanate—dextran. On the other hand, KM-H2 cells were shown to have variable-diversity-joining recombination of the immunoglobulin H gene, although they did not express any subclasses of immunoglobulin and they were negative for CD79a and CD79b. In addition, KM-H2 cells produced the messenger RNA of thePax-5 gene.These findings lead to a hypothesis that KM-H2 cells originated from the cells that had differentiated through the possible common DC—B-cell progenitors along the newly proposed pathway.

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References

  1. Diehl V, Von Kalle C, Fonatsch C, Tesch H, Juecker M, Schaadt M. The cell of origin in Hodgkin’s disease.Semin Oncol. 1990;17:660–672.

    PubMed  CAS  Google Scholar 

  2. Kadin ME, Stites DP, Levy R, Warnke R. Exogenous immunoglobulin and the macrophage origin of Reed-Sternberg cells in Hodgkin’s disease.N Engl J Med. 1978;299:1208–1214.

    Article  PubMed  CAS  Google Scholar 

  3. Kaplan H, Gartner S. ‘Sternberg-Reed’ giant cells of Hodgkin’s disease: cultivation in vitro, heterotransplantation, and characterization as neoplastic macrophages.Int J Cancer. 1977;19:511–525.

    Article  PubMed  CAS  Google Scholar 

  4. Delsol G, Meggetto F, Brousset P, et al. Relation of follicular dendritic reticulum cells to Reed-Sternberg cells of Hodgkin’s disease with emphasis on the expression of CD21 antigen.Am J Pathol. 1993;142:1729–1738.

    PubMed  PubMed Central  CAS  Google Scholar 

  5. Kadin ME. Possible origin of the Reed-Sternberg cell from an interdigitating reticulum cell.Cancer Treat Rep. 1982;66:601–608.

    PubMed  CAS  Google Scholar 

  6. Kennedy IC, Hart DN, Colls BM, Nimmo JC, Willis DA, Angus HB. Nodular sclerosing, mixed cellularity and lymphocyte-depleted variants of Hodgkin’s disease are probable dendritic cell malignancies.Clin Exp Immunol. 1989;76:324–331.

    PubMed  PubMed Central  CAS  Google Scholar 

  7. Nakamura S, Nagahama M, Kagami Y, et al. Hodgkin’s disease expressing follicular dendritic cell marker CD21 without any other B-cell marker.Am J Surg Pathol. 1999;23:363–376.

    Article  PubMed  CAS  Google Scholar 

  8. Kadin ME, Muramoto L, Said J. Expression of T-cell antigens on Reed-Sternberg cells in a subset of patients with nodular sclerosing and mixed cellularity of Hodgkin’s disease.Am J Pathol. 1988;130:345–353.

    PubMed  PubMed Central  CAS  Google Scholar 

  9. Schmid C, Pan L, Diss T, Isaacson PG. Expression of B-cell antigens by Hodgkin’s and Reed-Sternberg cells.Am J Pathol. 1991;139:701–707.

    PubMed  PubMed Central  CAS  Google Scholar 

  10. Stein H, Mason DY, O’Connor NTJ, et al. The expression of the Hodgkin’s disease-associated antigen Ki-1 in reactive and neoplastic lymphoid tissue: evidence that the Reed-Sternberg cells and histiocytic malignancies are derived from activated lymphoid cells.Blood. 1985;66:848–858.

    PubMed  CAS  Google Scholar 

  11. Stein H, Uchanska-Ziegler B, Gerdes J, Ziegler A, Wernet P. Hodgkin’s and Sternberg-Reed cells contain antigens specific to late cells of granulopoiesis.Int J Cancer. 1982;29:283–290.

    Article  PubMed  CAS  Google Scholar 

  12. Kamesaki H, Fukuhara S, Tatsumi E, et al. Cytochemical, immunologic, chromosomal, and molecular genetic analysis of a novel cell line derived from Hodgkin’s disease.Blood. 1986;68:285–292.

    PubMed  CAS  Google Scholar 

  13. Reid CDL, Stackpoole A, Meager A, Tikerpae J. Interactions of tumor necrosis factor with granulocyte-macrophage colony-stimulating factor and other cytokines in the regulation of dendritic cell growth in vitro from early bipotent CD34+ progenitors in human bone marrow.J Immunol. 1992;149:2681–2688.

    PubMed  CAS  Google Scholar 

  14. Banchereau J, Steinman RM. Dendritic cells and the control of immunity.Nature. 1998;392:245–252.

    Article  PubMed  CAS  Google Scholar 

  15. Steinman RM. The dendritic cell system and its role in immunogenicity.Annu Rev Immunol. 1991;9:271–296.

    Article  PubMed  CAS  Google Scholar 

  16. Zhou LJ, Tedder TF. Human blood dendritic cells selectively express CD83, a member of the immunoglobulin superfamily.J Immunol. 1995;154:3821–3835.

    PubMed  CAS  Google Scholar 

  17. Mosialos G, Birkenbach M, Ayehunie S, et al. Circulating human dendritic cells differentially express high levels of a 55-kd actinbundling protein.Am J Pathol. 1996;148:593–600.

    PubMed  PubMed Central  CAS  Google Scholar 

  18. Ross R, Ross XL, Schwing J, Langin T, Reske-Kunz AB. The actinbundling protein fascin is involved in the formation of dendritic processes in maturing epidermal Langerhans cells.J Immunol. 1998;160:3776–3782.

    PubMed  CAS  Google Scholar 

  19. Kato M, Neil TK, Clark GJ, Morris CM, Sorg RV, Hart DNJ. cDNA cloning of human DEC-205, a putative antigen-uptake receptor on dendritic cells.Immunogenetics. 1998;47:442–450.

    Article  PubMed  CAS  Google Scholar 

  20. Pinkus GS, Pinkus JL, Langhoff E, et al. Fascin, a sensitive new marker for Reed-Sternberg cells of Hodgkin’s disease.Am J Pathol. 1997;150:543–562.

    PubMed  PubMed Central  CAS  Google Scholar 

  21. Sorg UR, Morse TM, Patton WN, et al. Hodgkin’s cells express CD83, a dendritic cell lineage associated antigen.Pathology. 1997;29:294–299.

    Article  PubMed  CAS  Google Scholar 

  22. Gillis S, Watson J. Biochemical and biological characterization of lymphocyte regulatory molecules, V: Identification of an interleukin 2-producing human leukemia T cell line.J Exp Med. 1980;152:1709–1719.

    Article  PubMed  CAS  Google Scholar 

  23. Amakawa R, Fukuhara S, Ohno H, et al. Amplified and rearranged bcl-2 gene in two lymphoma cell lines, FL-218 and FL-318, carrying a 14;18 translocation.Cancer Res. 1990;50:2423–2428.

    PubMed  CAS  Google Scholar 

  24. Pulvertaft RJV. Cytology of Burkitt’s tumor (African lymphoma).Lancet. 1964;1:238–240.

    Article  PubMed  CAS  Google Scholar 

  25. Sallusto F, Lanzavecchia A. Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor-α.J Exp Med. 1994;179:1109–1118.

    Article  PubMed  CAS  Google Scholar 

  26. Hironaka T, Nagasaki M, Morikawa S, and Hirai K. Detection of Epstein-Barr virus transcripts in chemically or immunologically-activated cells and in a null cell-line (HLN-STL-C) by in situ hybridization with alkaline phosphatase-linked oligonucleotide probes.J Virol Methods. 1993;44:141–154.

    Article  PubMed  CAS  Google Scholar 

  27. Ito T, Inaba M, Inaba K, et al. A CD1a+/CD11c+ subset of human blood dendritic cells is a direct precursor of Langerhans cells.J Immunol. 1999;163:1409–1419.

    PubMed  CAS  Google Scholar 

  28. Tsoukas CD, Lambris JD. Expression of EBV/C3d receptors on T cells: biological significance.Immunol Today. 1993;14:56–59.

    Article  PubMed  CAS  Google Scholar 

  29. Liu YJ, Grouard G, de Bouteiller O, Banchereau J. Follicular dendritic cells and germinal centers.Int Rev Cytol. 1996;166:139–179.

    Article  PubMed  CAS  Google Scholar 

  30. Matsumoto M, Fu YX, Molina H, et al. Distinct roles of lymphotoxin alpha and the type 1 tumor necrosis factor (TNF) receptor in the establishment of follicular dendritic cells from non-bone marrow-derived cells.J Exp Med. 1997;186:1997–2004.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Chan JKC, Tsang WYW, Ng CS. Follicular dendritic cell tumor of oral cavity.Am J Surg Pathol. 1994;18:148–157.

    Article  PubMed  CAS  Google Scholar 

  32. Hollowood K, Stamp G, Zouvani I, Fletcher CDM. Extranodal follicular dendritic cell sarcoma of gastrointestinal tract.Am J Clin Pathol. 1995;103:90–97.

    Article  PubMed  CAS  Google Scholar 

  33. Pleiman CM, D’Ambrocio D, Cambier JC. The B-cell antigen receptor complex: structure and signal transduction.Immunol Today. 1994;15:393–399.

    Article  PubMed  CAS  Google Scholar 

  34. Bjorck P, Kincade PW. Cutting edge: CD19+ pro-B cells can give rise to dendritic cells in vitro.J Immunol. 1998;161:5795–5799.

    PubMed  CAS  Google Scholar 

  35. Nutt SL, Heavey B, Rolink AG, Busslinger M. Commitment to the B-lymphoid lineage depends on the transcription factor Pax5.Nature. 1999;401:556–562.

    Article  PubMed  CAS  Google Scholar 

  36. Delabie J, Tierens A, Gavriil T, Weisenburger DD, Chan WC. Phenotype, genotype and clonality of Reed-Sternberg cells in nodular sclerosis Hodgkin’s disease: results of a single-cell study.Br J Haematol. 1996;94:198–205.

    Article  PubMed  CAS  Google Scholar 

  37. Hummel M, Ziemann K, Lammert H, Pileri S, Sabattini E, Stein H. Hodgkin’s disease with monoclonal and polyclonal populations of Reed-Sternberg cells.N Engl J Med. 1995;333:901–906.

    Article  PubMed  CAS  Google Scholar 

  38. Kuppers R, Rajewsky K, Zhao M, et al. Hodgkin disease: Hodgkin and Reed-Sternberg cells picked from histological sections show clonal immunoglobulin gene rearrangements and appear to be derived from B cells at various stages of development.Proc Natl Acad Sci USA. 1994;91:10962–10966.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Foss HD, Reusch R, Demel G, et al. Frequent expression of the B-cell-specific activator protein in Reed-Sternberg cells of classical Hodgkin’s disease provides further evidence for its B-cell origin.Blood. 1999;94:3108–3113.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. First Department of Internal Medicine, Kansai Medical University, Osaka, Japan

    Kazutaka Uehira, Ryuichi Amakawa, Tomoki Ito, Tomoko Uehira, Yoshio Ozaki, Toshiki Shimizu, Masahiro Fujimoto & Shirou Fukuhara

  2. First Department of Pathology, Kansai Medical University, Osaka, Japan

    Muneo Inaba

Authors
  1. Kazutaka Uehira
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  2. Ryuichi Amakawa
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  3. Tomoki Ito
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  4. Tomoko Uehira
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  5. Yoshio Ozaki
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  6. Toshiki Shimizu
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  7. Masahiro Fujimoto
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  8. Muneo Inaba
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  9. Shirou Fukuhara
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Correspondence to Ryuichi Amakawa.

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Uehira, K., Amakawa, R., Ito, T. et al. A Hodgkin’s Disease Cell Line, KM-H2, Shows Biphenotypic Features of Dendritic Cells and B Cells. Int J Hematol 73, 236–244 (2001). https://doi.org/10.1007/BF02981944

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  • DOI: https://doi.org/10.1007/BF02981944

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