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. 1987 Apr 1;165(4):1188–1194. doi: 10.1084/jem.165.4.1188

Elevated myc expression and c-myc amplification in spontaneously occurring B lymphoid cell lines

PMCID: PMC2188571  PMID: 3549960

Abstract

Recently, a minor subpopulation of murine B lymphocytes, Ly-1+ B cells, has been distinguished by its unique ontogeny, tissue distribution, and prominence in certain autoimmune and neoplastic B cell diseases. We have previously described a simple murine spleen culture system that results in the spontaneous and exclusive outgrowth of long-term Ly-1+ B cell lines (B Ly-1 cells). Here, we report that the immortal growth property of B Ly-1 cells correlates with a 10-45-fold elevation of steady-state myc RNA and 2-10-fold amplification of the c-myc locus. While c-myc amplification has been observed in malignant cell lines derived from several tissues of origin, its occurrence in lymphoid cells has not been previously reported. The consistent c-myc amplification in B Ly-1 cells may reflect a unique state of this locus in the Ly-1+ B lymphocyte lineage, and contribute to the spontaneous immortalization of this B cell population in vitro, and its apparent predilection for malignant transformation in vivo.

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Selected References

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  1. Ault K. A., Antin J. H., Ginsburg D., Orkin S. H., Rappeport J. M., Keohan M. L., Martin P., Smith B. R. Phenotype of recovering lymphoid cell populations after marrow transplantation. J Exp Med. 1985 Jun 1;161(6):1483–1502. doi: 10.1084/jem.161.6.1483. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baines P., Dexter T. M., Schofield R. Characterization of malignant cell populations in MNU-induced leukaemia of mice. Leuk Res. 1979;3(1):23–28. doi: 10.1016/0145-2126(79)90005-5. [DOI] [PubMed] [Google Scholar]
  3. Braun J., Citri Y., Baltimore D., Forouzanpour F., King L., Teheranizadeh K., Bray M., Kliewer S. B-Ly1 cells: immortal Ly-1+ B lymphocyte cell lines spontaneously arising in murine splenic cultures. Immunol Rev. 1986 Oct;93:5–21. doi: 10.1111/j.1600-065x.1986.tb01499.x. [DOI] [PubMed] [Google Scholar]
  4. Braun J. Spontaneous in vitro occurrence and long-term culture of murine B lymphoblast cell lines. J Immunol. 1983 May;130(5):2113–2116. [PubMed] [Google Scholar]
  5. Caligaris-Cappio F., Janossy G. Surface markers in chronic lymphoid leukemias of B cell type. Semin Hematol. 1985 Jan;22(1):1–12. [PubMed] [Google Scholar]
  6. Campisi J., Gray H. E., Pardee A. B., Dean M., Sonenshein G. E. Cell-cycle control of c-myc but not c-ras expression is lost following chemical transformation. Cell. 1984 Feb;36(2):241–247. doi: 10.1016/0092-8674(84)90217-4. [DOI] [PubMed] [Google Scholar]
  7. Corcoran L. M., Adams J. M., Dunn A. R., Cory S. Murine T lymphomas in which the cellular myc oncogene has been activated by retroviral insertion. Cell. 1984 May;37(1):113–122. doi: 10.1016/0092-8674(84)90306-4. [DOI] [PubMed] [Google Scholar]
  8. Davidson W. F., Fredrickson T. N., Rudikoff E. K., Coffman R. L., Hartley J. W., Morse H. C., 3rd A unique series of lymphomas related to the Ly-1+ lineage of B lymphocyte differentiation. J Immunol. 1984 Aug;133(2):744–753. [PubMed] [Google Scholar]
  9. Favaloro J., Treisman R., Kamen R. Transcription maps of polyoma virus-specific RNA: analysis by two-dimensional nuclease S1 gel mapping. Methods Enzymol. 1980;65(1):718–749. doi: 10.1016/s0076-6879(80)65070-8. [DOI] [PubMed] [Google Scholar]
  10. Hayakawa K., Hardy R. R., Honda M., Herzenberg L. A., Steinberg A. D., Herzenberg L. A. Ly-1 B cells: functionally distinct lymphocytes that secrete IgM autoantibodies. Proc Natl Acad Sci U S A. 1984 Apr;81(8):2494–2498. doi: 10.1073/pnas.81.8.2494. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hayakawa K., Hardy R. R., Parks D. R., Herzenberg L. A. The "Ly-1 B" cell subpopulation in normal immunodefective, and autoimmune mice. J Exp Med. 1983 Jan 1;157(1):202–218. doi: 10.1084/jem.157.1.202. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hayward W. S., Neel B. G., Astrin S. M. Activation of a cellular onc gene by promoter insertion in ALV-induced lymphoid leukosis. Nature. 1981 Apr 9;290(5806):475–480. doi: 10.1038/290475a0. [DOI] [PubMed] [Google Scholar]
  13. Kelly K., Cochran B. H., Stiles C. D., Leder P. Cell-specific regulation of the c-myc gene by lymphocyte mitogens and platelet-derived growth factor. Cell. 1983 Dec;35(3 Pt 2):603–610. doi: 10.1016/0092-8674(83)90092-2. [DOI] [PubMed] [Google Scholar]
  14. Klein G., Klein E. Evolution of tumours and the impact of molecular oncology. Nature. 1985 May 16;315(6016):190–195. doi: 10.1038/315190a0. [DOI] [PubMed] [Google Scholar]
  15. Klinman D. M., Mushinski J. F., Honda M., Ishigatsubo Y., Mountz J. D., Raveche E. S., Steinberg A. D. Oncogene expression in autoimmune and normal peripheral blood mononuclear cells. J Exp Med. 1986 May 1;163(5):1292–1307. doi: 10.1084/jem.163.5.1292. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lanier L. L., Arnold L. W., Raybourne R. B., Russell S., Lynes M. A., Warner N. L., Haughton G. Transplantable B-cell lymphomas in B10. H-2aH-4bp/Wts mice. Immunogenetics. 1982;16(4):367–371. doi: 10.1007/BF00372309. [DOI] [PubMed] [Google Scholar]
  17. Lanier L. L., Warner N. L., Ledbetter J. A., Herzenberg L. A. Quantitative immunofluorescent analysis of surface phenotypes of murine B cell lymphomas and plasmacytomas with monoclonal antibodies. J Immunol. 1981 Oct;127(4):1691–1697. [PubMed] [Google Scholar]
  18. Manohar V., Brown E., Leiserson W. M., Chused T. M. Expression of Lyt-1 by a subset of B lymphocytes. J Immunol. 1982 Aug;129(2):532–538. [PubMed] [Google Scholar]
  19. Marcu K. B., Harris L. J., Stanton L. W., Erikson J., Watt R., Croce C. M. Transcriptionally active c-myc oncogene is contained within NIARD, a DNA sequence associated with chromosome translocations in B-cell neoplasia. Proc Natl Acad Sci U S A. 1983 Jan;80(2):519–523. doi: 10.1073/pnas.80.2.519. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Mushinski J. F., Bauer S. R., Potter M., Reddy E. P. Increased expression of myc-related oncogene mRNA characterizes most BALB/c plasmacytomas induced by pristane or Abelson murine leukemia virus. Proc Natl Acad Sci U S A. 1983 Feb;80(4):1073–1077. doi: 10.1073/pnas.80.4.1073. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Okumura K., Hayakawa K., Tada T. Cell-to-cell interaction controlled by immunoglobulin genes. Role of Thy-1-, Lyt-1+, Ig+ (B') cell in allotype-restricted antibody production. J Exp Med. 1982 Aug 1;156(2):443–453. doi: 10.1084/jem.156.2.443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Parnes J. R., Seidman J. G. Structure of wild-type and mutant mouse beta 2-microglobulin genes. Cell. 1982 Jun;29(2):661–669. doi: 10.1016/0092-8674(82)90182-9. [DOI] [PubMed] [Google Scholar]
  23. Payne G. S., Bishop J. M., Varmus H. E. Multiple arrangements of viral DNA and an activated host oncogene in bursal lymphomas. Nature. 1982 Jan 21;295(5846):209–214. doi: 10.1038/295209a0. [DOI] [PubMed] [Google Scholar]
  24. Perry R. P. Consequences of myc invasion of immunoglobulin loci: facts and speculation. Cell. 1983 Jul;33(3):647–649. doi: 10.1016/0092-8674(83)90006-5. [DOI] [PubMed] [Google Scholar]
  25. Plater-Zyberk C., Maini R. N., Lam K., Kennedy T. D., Janossy G. A rheumatoid arthritis B cell subset expresses a phenotype similar to that in chronic lymphocytic leukemia. Arthritis Rheum. 1985 Sep;28(9):971–976. doi: 10.1002/art.1780280903. [DOI] [PubMed] [Google Scholar]
  26. Selten G., Cuypers H. T., Zijlstra M., Melief C., Berns A. Involvement of c-myc in MuLV-induced T cell lymphomas in mice: frequency and mechanisms of activation. EMBO J. 1984 Dec 20;3(13):3215–3222. doi: 10.1002/j.1460-2075.1984.tb02281.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Stanton L. W., Watt R., Marcu K. B. Translocation, breakage and truncated transcripts of c-myc oncogene in murine plasmacytomas. Nature. 1983 Jun 2;303(5916):401–406. doi: 10.1038/303401a0. [DOI] [PubMed] [Google Scholar]

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