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. 1989 Apr;66(4):485–490.

The effect of leucyl-leucine methyl ester on proliferation and Ig secretion of EBV-transformed human B lymphocytes.

M Ohlin 1, L Danielsson 1, R Carlsson 1, C A Borrebaeck 1
PMCID: PMC1385146  PMID: 2541070

Abstract

The selective cytotoxicity of the lysosomotropic methyl esters of leucine or its lysosomal condensation product leucyl-leucine has been used to investigate the effect of cytolytic cells on the clonal outgrowth, cellular proliferation and antibody secretion of Epstein-Barr virus (EBV)-transformed human B cells. Large granular lymphocytes (LGL), monocytes, and a subset of T cells (CD8/CD11+) were permanently eliminated by the ester treatment. These lysosome-rich cells severely inhibit the clonal outgrowth of EBV-infected B cells, as determined by Poisson distribution calculations. Furthermore, leucyl-leucine methyl ester-treated and EBV-infected lymphocytes showed a significant increase in proliferative capability as well as immunoglobulin (Ig) production (three to 11 times) compared to non-treated but similarly infected lymphocytes. Since the effect of leucyl-leucine methyl ester treatment was also detectable in low-density (100 B cells/well) cultures, the suppression was unlikely to be exerted by EBV-specific T-cell clones, but pointed rather to the natural killer (NK) cells as effectors.

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Selected References

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

  1. Abruzzo L. V., Rowley D. A. Homeostasis of the antibody response: immunoregulation by NK cells. Science. 1983 Nov 11;222(4624):581–585. doi: 10.1126/science.6685343. [DOI] [PubMed] [Google Scholar]
  2. Arai S., Yamamoto H., Itoh K., Kumagai K. Suppressive effect of human natural killer cells on pokeweed mitogen-induced B cell differentiation. J Immunol. 1983 Aug;131(2):651–657. [PubMed] [Google Scholar]
  3. Bejarano M. T., Masucci M. G., Klein G., Klein E. T-cell-mediated inhibition of EBV-induced B-cell transformation: recognition of virus particles. Int J Cancer. 1988 Sep 15;42(3):359–364. doi: 10.1002/ijc.2910420309. [DOI] [PubMed] [Google Scholar]
  4. Borrebaeck C. A., Danielsson L., Möller S. A. Human monoclonal antibodies produced by primary in vitro immunization of peripheral blood lymphocytes. Proc Natl Acad Sci U S A. 1988 Jun;85(11):3995–3999. doi: 10.1073/pnas.85.11.3995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Borrebaeck C. A., Danielsson L., Möller S. A. Human monoclonal antibodies produced from L-leucine methyl ester-treated and in vitro immunized peripheral blood lymphocytes. Biochem Biophys Res Commun. 1987 Nov 13;148(3):941–946. doi: 10.1016/s0006-291x(87)80223-1. [DOI] [PubMed] [Google Scholar]
  6. Borrebaeck C. A. Human mAbs produced by primary in-vitro immunization. Immunol Today. 1988 Nov;9(11):355–359. doi: 10.1016/0167-5699(88)91337-0. [DOI] [PubMed] [Google Scholar]
  7. Callard R. E., Smith C. M. Histocompatibility requirements for T cell help in specific in vitro antibody responses to influenza virus by human blood lymphocytes. Eur J Immunol. 1981 Mar;11(3):206–212. doi: 10.1002/eji.1830110309. [DOI] [PubMed] [Google Scholar]
  8. Kleinerman E. S., Herberman R. B. Tumoricidal activity of human monocytes: evidence for cytolytic function distinct from that of NK cells. J Immunol. 1984 Jul;133(1):4–6. [PubMed] [Google Scholar]
  9. Kozbor D., Lagarde A. E., Roder J. C. Human hybridomas constructed with antigen-specific Epstein-Barr virus-transformed cell lines. Proc Natl Acad Sci U S A. 1982 Nov;79(21):6651–6655. doi: 10.1073/pnas.79.21.6651. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kuwano K., Arai S., Munakata T., Tomita Y., Yoshitake Y., Kumagai K. Suppressive effect of human natural killer cells on Epstein-Barr virus-induced immunoglobulin synthesis. J Immunol. 1986 Sep 1;137(5):1462–1468. [PubMed] [Google Scholar]
  11. Mason P. D., Weetman A. P., Sissons J. G., Borysiewicz L. K. Suppressive role of NK cells in pokeweed mitogen-induced immunoglobulin synthesis: effect of depletion/enrichment of Leu 11b+ cells. Immunology. 1988 Sep;65(1):113–118. [PMC free article] [PubMed] [Google Scholar]
  12. Masucci M. G., Bejarano M. T., Masucci G., Klein E. Large granular lymphocytes inhibit the in vitro growth of autologous Epstein-Barr virus-infected B cells. Cell Immunol. 1983 Mar;76(2):311–321. doi: 10.1016/0008-8749(83)90374-x. [DOI] [PubMed] [Google Scholar]
  13. Nabel G., Allard W. J., Cantor H. A cloned cell line mediating natural killer cell function inhibits immunoglobulin secretion. J Exp Med. 1982 Aug 1;156(2):658–663. doi: 10.1084/jem.156.2.658. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Rickinson A. B., Moss D. J., Pope J. H. Long-term C-cell-mediated immunity to Epstein-Barr virus in man. II. Components necessary for regression in virus-infected leukocyte cultures. Int J Cancer. 1979 May 15;23(5):610–617. doi: 10.1002/ijc.2910230505. [DOI] [PubMed] [Google Scholar]
  15. Seeley J. K., Masucci G., Poros A., Klein E., Golub S. H. Studies on cytotoxicity generated in human mixed lymphocyte cultures. II. Anti-K562 effectors are distinct from allospecific CTL and can be generated from NK-depleted T cells. J Immunol. 1979 Sep;123(3):1303–1311. [PubMed] [Google Scholar]
  16. Shope T. C., Kaplan J. Inhibition of the in vitro outgrowth of Epstein-Barr virus-infected lymphocytes by TG lymphocytes. J Immunol. 1979 Nov;123(5):2150–2155. [PubMed] [Google Scholar]
  17. Thiele D. L., Kurosaka M., Lipsky P. E. Phenotype of the accessory cell necessary for mitogen-stimulated T and B cell responses in human peripheral blood: delineation by its sensitivity to the lysosomotropic agent, L-leucine methyl ester. J Immunol. 1983 Nov;131(5):2282–2290. [PubMed] [Google Scholar]
  18. Thiele D. L., Lipsky P. E. Modulation of human natural killer cell function by L-leucine methyl ester: monocyte-dependent depletion from human peripheral blood mononuclear cells. J Immunol. 1985 Feb;134(2):786–793. [PubMed] [Google Scholar]
  19. Thiele D. L., Lipsky P. E. Regulation of cellular function by products of lysosomal enzyme activity: elimination of human natural killer cells by a dipeptide methyl ester generated from L-leucine methyl ester by monocytes or polymorphonuclear leukocytes. Proc Natl Acad Sci U S A. 1985 Apr;82(8):2468–2472. doi: 10.1073/pnas.82.8.2468. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Thiele D. L., Lipsky P. E. The immunosuppressive activity of L-leucyl-L-leucine methyl ester: selective ablation of cytotoxic lymphocytes and monocytes. J Immunol. 1986 Feb 1;136(3):1038–1048. [PubMed] [Google Scholar]
  21. Tosato G., Magrath I. T., Blaese R. M. T cell-mediated immunoregulation of Epstein Barr virus- (EBV) induced B lymphocyte activation in EBV-seropositive and EBV-seronegative individuals. J Immunol. 1982 Feb;128(2):575–579. [PubMed] [Google Scholar]

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