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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1986 Mar;83(5):1458–1462. doi: 10.1073/pnas.83.5.1458

Induction of c-myc expression in human B lymphocytes by B-cell growth factor and anti-immunoglobulin.

J Lacy, S N Sarkar, W C Summers
PMCID: PMC323095  PMID: 3513176

Abstract

Purified human B lymphocytes were examined for transcriptional expression of c-myc in response to mitogenic stimulation by the method of in situ hybridization using 35S-labeled DNA probes. The level of c-myc expression increased 10- to 20-fold within 2 hr after the addition of anti-mu, formalinized Staphylococcus aureus Cowan strain I, or B-cell growth factor, as compared to resting B cells. After 72-96 hr of mitogenic stimulation, c-myc expression remained elevated 5-fold, but expression among individual cells had become more heterogeneous than at early time points. To determine whether c-myc expression in human B lymphocytes is phase specific within the cell cycle, mitogen-stimulated cells were sorted by DNA content into populations of cells in G0/G1, S, and G2/M phases of the cell cycle. Examination of c-myc expression in phase-specific cells revealed that c-myc expression was elevated in all phases of the cell cycle, but it appeared to be maximally expressed in S phase. These studies suggest that c-myc expression in normal human B lymphocytes is cell-cycle dependent and remains elevated in all phases of the cycling cell.

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Selected References

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  1. Boyd A. W., Anderson K. C., Freedman A. S., Fisher D. C., Slaughenhoupt B., Schlossman S. F., Nadler L. M. Studies of in vitro activation and differentiation of human B lymphocytes. I. Phenotypic and functional characterization of the B cell population responding to anti-Ig antibody. J Immunol. 1985 Mar;134(3):1516–1523. [PubMed] [Google Scholar]
  2. Crissman H. A., Tobey R. A. Cell-cycle analysis in 20 minutes. Science. 1974 Jun 21;184(4143):1297–1298. doi: 10.1126/science.184.4143.1297. [DOI] [PubMed] [Google Scholar]
  3. Dalla-Favera R., Wong-Staal F., Gallo R. C. Onc gene amplification in promyelocytic leukaemia cell line HL-60 and primary leukaemic cells of the same patient. Nature. 1982 Sep 2;299(5878):61–63. doi: 10.1038/299061a0. [DOI] [PubMed] [Google Scholar]
  4. Ellis R. W., Defeo D., Shih T. Y., Gonda M. A., Young H. A., Tsuchida N., Lowy D. R., Scolnick E. M. The p21 src genes of Harvey and Kirsten sarcoma viruses originate from divergent members of a family of normal vertebrate genes. Nature. 1981 Aug 6;292(5823):506–511. doi: 10.1038/292506a0. [DOI] [PubMed] [Google Scholar]
  5. Erikson J., ar-Rushdi A., Drwinga H. L., Nowell P. C., Croce C. M. Transcriptional activation of the translocated c-myc oncogene in burkitt lymphoma. Proc Natl Acad Sci U S A. 1983 Feb;80(3):820–824. doi: 10.1073/pnas.80.3.820. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Glazer P. M., Summers W. C. Oncogene expression in isogenic, EBV-positive and -negative Burkitt lymphoma cell lines. Intervirology. 1985;23(2):82–89. doi: 10.1159/000149589. [DOI] [PubMed] [Google Scholar]
  7. Hann S. R., Thompson C. B., Eisenman R. N. c-myc oncogene protein synthesis is independent of the cell cycle in human and avian cells. 1985 Mar 28-Apr 3Nature. 314(6009):366–369. doi: 10.1038/314366a0. [DOI] [PubMed] [Google Scholar]
  8. Hogan B. L., Taylor A., Adamson E. Cell interactions modulate embryonal carcinoma cell differentiation into parietal or visceral endoderm. Nature. 1981 May 21;291(5812):235–237. doi: 10.1038/291235a0. [DOI] [PubMed] [Google Scholar]
  9. Jelinek D. F., Lipsky P. E. The roles of T cell factors in activation, cell cycle progression, and differentiation of human B cells. J Immunol. 1985 Mar;134(3):1690–1701. [PubMed] [Google Scholar]
  10. Kaczmarek L., Hyland J. K., Watt R., Rosenberg M., Baserga R. Microinjected c-myc as a competence factor. Science. 1985 Jun 14;228(4705):1313–1315. doi: 10.1126/science.4001943. [DOI] [PubMed] [Google Scholar]
  11. Kehrl J. H., Muraguchi A., Butler J. L., Falkoff R. J., Fauci A. S. Human B cell activation, proliferation and differentiation. Immunol Rev. 1984 Apr;78:75–96. doi: 10.1111/j.1600-065x.1984.tb00477.x. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Lacy J., Summers W. C., Canellakis Z. N. Effects of diacetyl diamines on in vitro activation and proliferation of human B lymphocytes. J Immunol. 1985 Dec;135(6):3772–3776. [PubMed] [Google Scholar]
  14. Land H., Parada L. F., Weinberg R. A. Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes. Nature. 1983 Aug 18;304(5927):596–602. doi: 10.1038/304596a0. [DOI] [PubMed] [Google Scholar]
  15. Leder P., Battey J., Lenoir G., Moulding C., Murphy W., Potter H., Stewart T., Taub R. Translocations among antibody genes in human cancer. Science. 1983 Nov 18;222(4625):765–771. doi: 10.1126/science.6356357. [DOI] [PubMed] [Google Scholar]
  16. Mage M. G., McHugh L. L., Rothstein T. L. Mouse lymphocytes with and without surface immunoglobulin: preparative scale separation in polystyrene tissue culture dishes coated with specifically purified anti-immunoglobulin. J Immunol Methods. 1977;15(1):47–56. doi: 10.1016/0022-1759(77)90016-3. [DOI] [PubMed] [Google Scholar]
  17. Maizel A. L., Morgan J. W., Mehta S. R., Kouttab N. M., Bator J. M., Sahasrabuddhe C. G. Long-term growth of human B cells and their use in a microassay for B-cell growth factor. Proc Natl Acad Sci U S A. 1983 Aug;80(16):5047–5051. doi: 10.1073/pnas.80.16.5047. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Menezes J., Leibold W., Klein G., Clements G. Establishment and characterization of an Epstein-Barr virus (EBC)-negative lymphoblastoid B cell line (BJA-B) from an exceptional, EBV-genome-negative African Burkitt's lymphoma. Biomedicine. 1975 Jul;22(4):276–284. [PubMed] [Google Scholar]
  19. Muraguchi A., Kehrl J. H., Butler J. L., Fauci A. S. Sequential requirements for cell cycle progression of resting human B cells after activation by anti-Ig. J Immunol. 1984 Jan;132(1):176–180. [PubMed] [Google Scholar]
  20. 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]
  21. Reddy E. P., Reynolds R. K., Watson D. K., Schultz R. A., Lautenberger J., Papas T. S. Nucleotide sequence analysis of the proviral genome of avian myelocytomatosis virus (MC29). Proc Natl Acad Sci U S A. 1983 May;80(9):2500–2504. doi: 10.1073/pnas.80.9.2500. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Reitsma P. H., Rothberg P. G., Astrin S. M., Trial J., Bar-Shavit Z., Hall A., Teitelbaum S. L., Kahn A. J. Regulation of myc gene expression in HL-60 leukaemia cells by a vitamin D metabolite. Nature. 1983 Dec 1;306(5942):492–494. doi: 10.1038/306492a0. [DOI] [PubMed] [Google Scholar]
  23. Shih C., Weinberg R. A. Isolation of a transforming sequence from a human bladder carcinoma cell line. Cell. 1982 May;29(1):161–169. doi: 10.1016/0092-8674(82)90100-3. [DOI] [PubMed] [Google Scholar]
  24. Strickland S., Mahdavi V. The induction of differentiation in teratocarcinoma stem cells by retinoic acid. Cell. 1978 Oct;15(2):393–403. doi: 10.1016/0092-8674(78)90008-9. [DOI] [PubMed] [Google Scholar]
  25. Taub R., Kirsch I., Morton C., Lenoir G., Swan D., Tronick S., Aaronson S., Leder P. Translocation of the c-myc gene into the immunoglobulin heavy chain locus in human Burkitt lymphoma and murine plasmacytoma cells. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7837–7841. doi: 10.1073/pnas.79.24.7837. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Thompson C. B., Challoner P. B., Neiman P. E., Groudine M. Levels of c-myc oncogene mRNA are invariant throughout the cell cycle. 1985 Mar 28-Apr 3Nature. 314(6009):363–366. doi: 10.1038/314363a0. [DOI] [PubMed] [Google Scholar]
  27. Venezky D. L., Angerer L. M., Angerer R. C. Accumulation of histone repeat transcripts in the sea urchin egg pronucleus. Cell. 1981 May;24(2):385–391. doi: 10.1016/0092-8674(81)90328-7. [DOI] [PubMed] [Google Scholar]
  28. Vennström B., Bishop J. M. Isolation and characterization of chicken DNA homologous to the two putative oncogenes of avian erythroblastosis virus. Cell. 1982 Jan;28(1):135–143. doi: 10.1016/0092-8674(82)90383-x. [DOI] [PubMed] [Google Scholar]
  29. ar-Rushdi A., Nishikura K., Erikson J., Watt R., Rovera G., Croce C. M. Differential expression of the translocated and the untranslocated c-myc oncogene in Burkitt lymphoma. Science. 1983 Oct 28;222(4622):390–393. doi: 10.1126/science.6414084. [DOI] [PubMed] [Google Scholar]

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