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. 1990 Sep;137(3):517–522.

Characterization of Epstein-Barr virus-induced lymphoproliferation derived from human peripheral blood mononuclear cells transferred to severe combined immunodeficient mice.

M Okano 1, Y Taguchi 1, H Nakamine 1, S J Pirruccello 1, J R Davis 1, K W Beisel 1, K L Kleveland 1, W G Sanger 1, R R Fordyce 1, D T Purtilo 1
PMCID: PMC1877520  PMID: 1975985

Abstract

Mice with severe combined immunodeficiency (SCID) received 6 X 10(7) fresh human peripheral blood mononuclear cells (PBMC) intraperitoneally from Epstein-Barr virus (EBV)-seropositive and -seronegative donors. B95-8 EBV was inoculated intraperitoneally and intravenously to the mice 6 weeks after transfer of seronegative PBMC. Three of four mice transferred with PBMC from two EBV-seropositive donors and two of four mice from two EBV-seronegative donors inoculated with EBV developed fatal EBV-induced lymphoproliferative disease within 6 to 10 weeks. These tumors were oligoclonal or polyclonal by cytoplasmic immunoglobulin expression. Furthermore no consistent clonal chromosomal abnormalities were shown. Cell lines established from these tumors showed low cloning efficiency in soft agarose. In addition, latent membrane protein, B-lymphocyte activation antigen (CD23), and cell-adhesion molecules (ICAM-1, CD18) all were expressed in the EBV-positive infiltrating lymphoproliferative lesions in each mouse. These results suggest that lymphoid tumors are comparable to lymphoblastoid cell lines immortalized by EBV and are not malignant lymphomas such as Burkitt's lymphoma. This model may be useful for investigating mechanisms responsible for the growing numbers of lymphoproliferative diseases that are occurring in patients with inherited or acquired immunodeficiencies.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bosma G. C., Custer R. P., Bosma M. J. A severe combined immunodeficiency mutation in the mouse. Nature. 1983 Feb 10;301(5900):527–530. doi: 10.1038/301527a0. [DOI] [PubMed] [Google Scholar]
  2. Cannon M. J., Pisa P., Fox R. I., Cooper N. R. Epstein-Barr virus induces aggressive lymphoproliferative disorders of human B cell origin in SCID/hu chimeric mice. J Clin Invest. 1990 Apr;85(4):1333–1337. doi: 10.1172/JCI114573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cleary M. L., Epstein M. A., Finerty S., Dorfman R. F., Bornkamm G. W., Kirkwood J. K., Morgan A. J., Sklar J. Individual tumors of multifocal EB virus-induced malignant lymphomas in tamarins arise from different B-cell clones. Science. 1985 May 10;228(4700):722–724. doi: 10.1126/science.2986287. [DOI] [PubMed] [Google Scholar]
  4. Davey D. D., Kamat D., Laszewski M., Goeken J. A., Kemp J. D., Trigg M. E., Purtilo D. T., Davis J., Dick F. R. Epstein-Barr virus-related lymphoproliferative disorders following bone marrow transplantation: an immunologic and genotypic analysis. Mod Pathol. 1989 Jan;2(1):27–34. [PubMed] [Google Scholar]
  5. Frizzera G., Hanto D. W., Gajl-Peczalska K. J., Rosai J., McKenna R. W., Sibley R. K., Holahan K. P., Lindquist L. L. Polymorphic diffuse B-cell hyperplasias and lymphomas in renal transplant recipients. Cancer Res. 1981 Nov;41(11 Pt 1):4262–4279. [PubMed] [Google Scholar]
  6. Johnson D. R., Wolfe L. G., Levan G., Klein G., Ernberg I., Aman P. Epstein-Barr virus (EBV)-induced lymphoproliferative disease in cotton-topped marmosets. Int J Cancer. 1983 Jan 15;31(1):91–97. doi: 10.1002/ijc.2910310115. [DOI] [PubMed] [Google Scholar]
  7. Miller G., Lipman M. Release of infectious Epstein-Barr virus by transformed marmoset leukocytes. Proc Natl Acad Sci U S A. 1973 Jan;70(1):190–194. doi: 10.1073/pnas.70.1.190. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Mosier D. E., Gulizia R. J., Baird S. M., Wilson D. B. Transfer of a functional human immune system to mice with severe combined immunodeficiency. Nature. 1988 Sep 15;335(6187):256–259. doi: 10.1038/335256a0. [DOI] [PubMed] [Google Scholar]
  9. Nilsson K., Giovanella B. C., Stehlin J. S., Klein G. Tumorigenicity of human hematopoietic cell lines in athymic nude mice. Int J Cancer. 1977 Mar 15;19(3):337–344. doi: 10.1002/ijc.2910190309. [DOI] [PubMed] [Google Scholar]
  10. Nilsson K., Pontén J. Classification and biological nature of established human hematopoietic cell lines. Int J Cancer. 1975 Feb 15;15(2):321–341. doi: 10.1002/ijc.2910150217. [DOI] [PubMed] [Google Scholar]
  11. Okano M., Pirruccello S. J., Grierson H. L., Johnson D. R., Thiele G. M., Purtilo D. T. Immunovirological studies of fatal infectious mononucleosis in a patient with X-linked lymphoproliferative syndrome treated with intravenous immunoglobulin and interferon-alpha. Clin Immunol Immunopathol. 1990 Mar;54(3):410–418. doi: 10.1016/0090-1229(90)90054-t. [DOI] [PubMed] [Google Scholar]
  12. Okano M., Thiele G. M., Davis J. R., Grierson H. L., Purtilo D. T. Epstein-Barr virus and human diseases: recent advances in diagnosis. Clin Microbiol Rev. 1988 Jul;1(3):300–312. doi: 10.1128/cmr.1.3.300. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Seabright M. A rapid banding technique for human chromosomes. Lancet. 1971 Oct 30;2(7731):971–972. doi: 10.1016/s0140-6736(71)90287-x. [DOI] [PubMed] [Google Scholar]
  14. Shapiro R. S., McClain K., Frizzera G., Gajl-Peczalska K. J., Kersey J. H., Blazar B. R., Arthur D. C., Patton D. F., Greenberg J. S., Burke B. Epstein-Barr virus associated B cell lymphoproliferative disorders following bone marrow transplantation. Blood. 1988 May;71(5):1234–1243. [PubMed] [Google Scholar]
  15. Steel C. M., Woodward M. A., Davidson C., Philipson J., Arthur E. Non-random chromosome gains in human lymphoblastoid cell lines. Nature. 1977 Nov 24;270(5635):349–351. doi: 10.1038/270349a0. [DOI] [PubMed] [Google Scholar]
  16. Young L., Alfieri C., Hennessy K., Evans H., O'Hara C., Anderson K. C., Ritz J., Shapiro R. S., Rickinson A., Kieff E. Expression of Epstein-Barr virus transformation-associated genes in tissues of patients with EBV lymphoproliferative disease. N Engl J Med. 1989 Oct 19;321(16):1080–1085. doi: 10.1056/NEJM198910193211604. [DOI] [PubMed] [Google Scholar]

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