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. 1989 Jul;84(1):236–243. doi: 10.1172/JCI114146

Production of lymphotoxin by isolated human tonsillar B lymphocytes and B lymphocyte cell lines.

S S Sung 1, L K Jung 1, J A Walters 1, E W Jeffes 3rd 1, G A Granger 1, S M Fu 1
PMCID: PMC303975  PMID: 2786889

Abstract

The expression of lymphotoxin (LT) mRNA and cytokine in human tonsillar B cells and B cell lines was examined by Northern blots and cytotoxicity assays, respectively. In tonsillar B cells, phorbol myristate acetate (PMA) or Staphylococcus aureus Cowan l (SAC) alone induced low levels of LT mRNA accumulation. However, SAC and anti-mu were strongly synergistic with PMA in this induction. Peak LT mRNA expression in tonsillar B cells stimulated by PMA plus SAC occurred between 48 and 72 h and was approximately half as much as that in PMA plus anti-CD3-stimulated T cells. Cyclosporine A was not effective in inhibiting LT mRNA accumulation by stimulated tonsillar B cells. A number of B cell lines could also be stimulated by PMA to express LT mRNA. Peak accumulation of LT mRNA in the cell line RPMI 1788 stimulated with PMA peaked about 8 h. A23187 in combination with PMA caused this accumulation to increase slightly and to peak earlier. The cytotoxic effects in the supernatants of stimulated B cells were contributed mostly by LT. The results indicate that tonsillar B cells are important in LT production and that there are important differences in the stimulation requirements for LT production and in LT mRNA expression kinetics between tonsillar B cells and B cell lines.

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Selected References

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

  1. Averbook B. J., Yamamoto R. S., Ulich T. R., Jeffes E. W., Masunaka I., Granger G. A. Purified native and recombinant human alpha lymphotoxin [tumor necrosis factor (TNF)-beta] induces inflammatory reactions in normal skin. J Clin Immunol. 1987 Jul;7(4):333–340. doi: 10.1007/BF00915556. [DOI] [PubMed] [Google Scholar]
  2. Bersani L., Colotta F., Peri G., Mantovani A. Cytotoxic effector function of B lymphoblasts. J Immunol. 1987 Jul 15;139(2):645–648. [PubMed] [Google Scholar]
  3. Beutler B., Cerami A. The common mediator of shock, cachexia, and tumor necrosis. Adv Immunol. 1988;42:213–231. doi: 10.1016/s0065-2776(08)60846-9. [DOI] [PubMed] [Google Scholar]
  4. Broudy V. C., Harlan J. M., Adamson J. W. Disparate effects of tumor necrosis factor-alpha/cachectin and tumor necrosis factor-beta/lymphotoxin on hematopoietic growth factor production and neutrophil adhesion molecule expression by cultured human endothelial cells. J Immunol. 1987 Jun 15;138(12):4298–4302. [PubMed] [Google Scholar]
  5. Cambier J. C., Ransom J. T. Molecular mechanisms of transmembrane signaling in B lymphocytes. Annu Rev Immunol. 1987;5:175–199. doi: 10.1146/annurev.iy.05.040187.001135. [DOI] [PubMed] [Google Scholar]
  6. Ferrante A., Nandoskar M., Bates E. J., Goh D. H., Beard L. J. Tumour necrosis factor beta (lymphotoxin) inhibits locomotion and stimulates the respiratory burst and degranulation of neutrophils. Immunology. 1988 Mar;63(3):507–512. [PMC free article] [PubMed] [Google Scholar]
  7. Garrett I. R., Durie B. G., Nedwin G. E., Gillespie A., Bringman T., Sabatini M., Bertolini D. R., Mundy G. R. Production of lymphotoxin, a bone-resorbing cytokine, by cultured human myeloma cells. N Engl J Med. 1987 Aug 27;317(9):526–532. doi: 10.1056/NEJM198708273170902. [DOI] [PubMed] [Google Scholar]
  8. Granelli-Piperno A., Keane M., Steinman R. M. Evidence that cyclosporine inhibits cell-mediated immunity primarily at the level of the T lymphocyte rather than the accessory cell. Transplantation. 1988 Aug;46(2 Suppl):53S–60S. doi: 10.1097/00007890-198808001-00011. [DOI] [PubMed] [Google Scholar]
  9. Granger G. A., Orr S. L., Yamamoto R. S. Lymphotoxins, macrophage cytotoxins, and tumor necrosis factors: an interrelated family of antitumor effector molecules. J Clin Immunol. 1985 Jul;5(4):217–219. doi: 10.1007/BF00929455. [DOI] [PubMed] [Google Scholar]
  10. Granger G. A., Williams T. W. Lymphocyte cytotoxicity in vitro: activation and release of a cytotoxic factor. Nature. 1968 Jun 29;218(5148):1253–1254. doi: 10.1038/2181253a0. [DOI] [PubMed] [Google Scholar]
  11. Jeffes E. W., Yamamoto R. S., Ahmed A. R., Granger G. A. Lymphotoxin detected in the blister fluid of bullous pemphigoid patients. J Clin Immunol. 1984 Jan;4(1):31–35. doi: 10.1007/BF00915284. [DOI] [PubMed] [Google Scholar]
  12. June C. H., Ledbetter J. A., Gillespie M. M., Lindsten T., Thompson C. B. T-cell proliferation involving the CD28 pathway is associated with cyclosporine-resistant interleukin 2 gene expression. Mol Cell Biol. 1987 Dec;7(12):4472–4481. doi: 10.1128/mcb.7.12.4472. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kawano M., Hirano T., Matsuda T., Taga T., Horii Y., Iwato K., Asaoku H., Tang B., Tanabe O., Tanaka H. Autocrine generation and requirement of BSF-2/IL-6 for human multiple myelomas. Nature. 1988 Mar 3;332(6159):83–85. doi: 10.1038/332083a0. [DOI] [PubMed] [Google Scholar]
  14. Kehrl J. H., Alvarez-Mon M., Delsing G. A., Fauci A. S. Lymphotoxin is an important T cell-derived growth factor for human B cells. Science. 1987 Nov 20;238(4830):1144–1146. doi: 10.1126/science.3500512. [DOI] [PubMed] [Google Scholar]
  15. Kehrl J. H., Miller A., Fauci A. S. Effect of tumor necrosis factor alpha on mitogen-activated human B cells. J Exp Med. 1987 Sep 1;166(3):786–791. doi: 10.1084/jem.166.3.786. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Locksley R. M., Heinzel F. P., Shepard H. M., Agosti J., Eessalu T. E., Aggarwal B. B., Harlan J. M. Tumor necrosis factors alpha and beta differ in their capacities to generate interleukin 1 release from human endothelial cells. J Immunol. 1987 Sep 15;139(6):1891–1895. [PubMed] [Google Scholar]
  17. Lotz M., Tsoukas C. D., Fong S., Dinarello C. A., Carson D. A., Vaughan J. H. Release of lymphokines after Epstein Barr virus infection in vitro. I. Sources of and kinetics of production of interferons and interleukins in normal humans. J Immunol. 1986 May 15;136(10):3636–3642. [PubMed] [Google Scholar]
  18. Matsushima K., Procopio A., Abe H., Scala G., Ortaldo J. R., Oppenheim J. J. Production of interleukin 1 activity by normal human peripheral blood B lymphocytes. J Immunol. 1985 Aug;135(2):1132–1136. [PubMed] [Google Scholar]
  19. Muraguchi A., Hirano T., Tang B., Matsuda T., Horii Y., Nakajima K., Kishimoto T. The essential role of B cell stimulatory factor 2 (BSF-2/IL-6) for the terminal differentiation of B cells. J Exp Med. 1988 Feb 1;167(2):332–344. doi: 10.1084/jem.167.2.332. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Nedospasov S. A., Shakhov A. N., Turetskaya R. L., Mett V. A., Azizov M. M., Georgiev G. P., Korobko V. G., Dobrynin V. N., Filippov S. A., Bystrov N. S. Tandem arrangement of genes coding for tumor necrosis factor (TNF-alpha) and lymphotoxin (TNF-beta) in the human genome. Cold Spring Harb Symp Quant Biol. 1986;51(Pt 1):611–624. doi: 10.1101/sqb.1986.051.01.073. [DOI] [PubMed] [Google Scholar]
  21. Paul N. L., Ruddle N. H. Lymphotoxin. Annu Rev Immunol. 1988;6:407–438. doi: 10.1146/annurev.iy.06.040188.002203. [DOI] [PubMed] [Google Scholar]
  22. Ruddle N. H., Waksman B. H. Cytotoxic effect of lymphocyte-antigen interaction in delayed hypersensitivity. Science. 1967 Sep 1;157(3792):1060–1062. doi: 10.1126/science.157.3792.1060. [DOI] [PubMed] [Google Scholar]
  23. Shalaby M. R., Espevik T., Rice G. C., Ammann A. J., Figari I. S., Ranges G. E., Palladino M. A., Jr The involvement of human tumor necrosis factors-alpha and -beta in the mixed lymphocyte reaction. J Immunol. 1988 Jul 15;141(2):499–503. [PubMed] [Google Scholar]
  24. Shevach E. M. The effects of cyclosporin A on the immune system. Annu Rev Immunol. 1985;3:397–423. doi: 10.1146/annurev.iy.03.040185.002145. [DOI] [PubMed] [Google Scholar]
  25. Sung S. S., Jung L. K., Walters J. A., Chen W., Wang C. Y., Fu S. M. Production of tumor necrosis factor/cachectin by human B cell lines and tonsillar B cells. J Exp Med. 1988 Nov 1;168(5):1539–1551. doi: 10.1084/jem.168.5.1539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Weiss A., Imboden J., Hardy K., Manger B., Terhorst C., Stobo J. The role of the T3/antigen receptor complex in T-cell activation. Annu Rev Immunol. 1986;4:593–619. doi: 10.1146/annurev.iy.04.040186.003113. [DOI] [PubMed] [Google Scholar]
  27. Wong G. H., Goeddel D. V. Tumour necrosis factors alpha and beta inhibit virus replication and synergize with interferons. 1986 Oct 30-Nov 5Nature. 323(6091):819–822. doi: 10.1038/323819a0. [DOI] [PubMed] [Google Scholar]

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