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. 1990 Apr;85(4):1333–1337. doi: 10.1172/JCI114573

Epstein-Barr virus induces aggressive lymphoproliferative disorders of human B cell origin in SCID/hu chimeric mice.

M J Cannon 1, P Pisa 1, R I Fox 1, N R Cooper 1
PMCID: PMC296572  PMID: 2156900

Abstract

C.B-17 scid mice were reconstituted by intraperitoneal injection of human tonsil cells or PBL from EBV-seronegative donors. Subsequent injection of EBV resulted in the rapid development (within 19-33 d) of aggressive, fatal, lymphoproliferative disorders of human B cell origin. Autopsies revealed solid tumors in the abdomen, and occasionally in the liver, thymus, or spleen. Histopathologic analysis showed that the tumors were high-grade immunoblastic lymphomas and FACS analyses of tumor cells indicated that they were of human B-lymphoid origin. The tumor cells grew in vitro and induced new tumors on injection into severe combined immunodeficient (SCID) mice. Karyotypic analysis and Southern blots for c-myc or bcl-2 rearrangements revealed no chromosomal abnormalities and translocations. Southern blot analysis also showed that the cells possessed EBV DNA sequences. Although these tumors undoubtedly reflect infection of the transferred B cells with EBV in vivo, intraperitoneal transfer of short-term lymphoid cell lines transformed in vitro with EBV resulted in ascites production without evidence of tumor formation.

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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. 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]
  3. Cleary M. L., Nalesnik M. A., Shearer W. T., Sklar J. Clonal analysis of transplant-associated lymphoproliferations based on the structure of the genomic termini of the Epstein-Barr virus. Blood. 1988 Jul;72(1):349–352. [PubMed] [Google Scholar]
  4. Cleary M. L., Warnke R., Sklar J. Monoclonality of lymphoproliferative lesions in cardiac-transplant recipients. Clonal analysis based on immunoglobulin-gene rearrangements. N Engl J Med. 1984 Feb 23;310(8):477–482. doi: 10.1056/NEJM198402233100801. [DOI] [PubMed] [Google Scholar]
  5. Dambaugh T., Beisel C., Hummel M., King W., Fennewald S., Cheung A., Heller M., Raab-Traub N., Kieff E. Epstein-Barr virus (B95-8) DNA VII: molecular cloning and detailed mapping. Proc Natl Acad Sci U S A. 1980 May;77(5):2999–3003. doi: 10.1073/pnas.77.5.2999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fox R. I., Pearson G., Vaughan J. H. Detection of Epstein-Barr virus-associated antigens and DNA in salivary gland biopsies from patients with Sjogren's syndrome. J Immunol. 1986 Nov 15;137(10):3162–3168. [PubMed] [Google Scholar]
  7. 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]
  8. Gaston J. S., Rickinson A. B., Epstein M. A. Epstein-Barr-virus-specific T-cell memory in renal-allograft recipients under long-term immunosuppression. Lancet. 1982 Apr 24;1(8278):923–925. doi: 10.1016/s0140-6736(82)91930-4. [DOI] [PubMed] [Google Scholar]
  9. Gregory C. D., Murray R. J., Edwards C. F., Rickinson A. B. Downregulation of cell adhesion molecules LFA-3 and ICAM-1 in Epstein-Barr virus-positive Burkitt's lymphoma underlies tumor cell escape from virus-specific T cell surveillance. J Exp Med. 1988 Jun 1;167(6):1811–1824. doi: 10.1084/jem.167.6.1811. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hamilton-Dutoit S. J., Pallesen G., Karkov J., Skinhøj P., Franzmann M. B., Pedersen C. Identification of EBV-DNA in tumour cells of AIDS-related lymphomas by in-situ hybridisation. Lancet. 1989 Mar 11;1(8637):554–552. doi: 10.1016/s0140-6736(89)90093-7. [DOI] [PubMed] [Google Scholar]
  11. Hanto D. W., Frizzera G., Gajl-Peczalska K. J., Simmons R. L. Epstein-Barr virus, immunodeficiency, and B cell lymphoproliferation. Transplantation. 1985 May;39(5):461–472. doi: 10.1097/00007890-198505000-00001. [DOI] [PubMed] [Google Scholar]
  12. Hanto D. W., Gajl-Peczalska K. J., Frizzera G., Arthur D. C., Balfour H. H., Jr, McClain K., Simmons R. L., Najarian J. S. Epstein-Barr virus (EBV) induced polyclonal and monoclonal B-cell lymphoproliferative diseases occurring after renal transplantation. Clinical, pathologic, and virologic findings and implications for therapy. Ann Surg. 1983 Sep;198(3):356–369. doi: 10.1097/00000658-198309000-00012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. 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]
  15. 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]
  16. Pelicci P. G., Knowles D. M., 2nd, Arlin Z. A., Wieczorek R., Luciw P., Dina D., Basilico C., Dalla-Favera R. Multiple monoclonal B cell expansions and c-myc oncogene rearrangements in acquired immune deficiency syndrome-related lymphoproliferative disorders. Implications for lymphomagenesis. J Exp Med. 1986 Dec 1;164(6):2049–2060. doi: 10.1084/jem.164.6.2049. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Rickinson A. B., Rowe M., Hart I. J., Yao Q. Y., Henderson L. E., Rabin H., Epstein M. A. T-cell-mediated regression of "spontaneous" and of Epstein-Barr virus-induced B-cell transformation in vitro: studies with cyclosporin A. Cell Immunol. 1984 Sep;87(2):646–658. doi: 10.1016/0008-8749(84)90032-7. [DOI] [PubMed] [Google Scholar]

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