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. 1990 Feb;79(2):240–245. doi: 10.1111/j.1365-2249.1990.tb05185.x

Effects of a novel immunosuppressive agent, FK506, on human B cell activation.

N Suzuki 1, T Sakane 1, T Tsunematsu 1
PMCID: PMC1534763  PMID: 1690097

Abstract

We examined the effect of new immunosuppressive agent, FK506, on the human B cell function, in comparison with that of cyclosporin A (CyA) and tried to define the discrete activation step(s) which is selectively affected by FK506 and CyA. We used polyclonal B cell activators, Staphylococcus aureus Cowan I (SAC) and pokeweed mitogen (PWM). We found that (i) the initial B cell activation process by PWM, which is on the basis of T cell-dependent manner, is susceptible to the inhibitory effects of FK506 and CyA, while initial B cell activation on the basis of T cell-independent manner by SAC is resistant to these drugs; (ii) they also inhibit helper factor production by T cells; (iii) once they are activated, the B cells become resistant to inhibition by the drugs; and (iv) on an equimolar basis, FK506 exhibits 100-fold greater inhibitory activity than does CyA. Thus FK506 mainly interferes with interactions between T cells and other cells which are essential for B cell activation process, resulting in inhibition of B cell function.

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Selected References

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

  1. Bickel M., Tsuda H., Amstad P., Evequoz V., Mergenhagen S. E., Wahl S. M., Pluznik D. H. Differential regulation of colony-stimulating factors and interleukin 2 production by cyclosporin A. Proc Natl Acad Sci U S A. 1987 May;84(10):3274–3277. doi: 10.1073/pnas.84.10.3274. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Borel J. F., Feurer C., Magnée C., Stähelin H. Effects of the new anti-lymphocytic peptide cyclosporin A in animals. Immunology. 1977 Jun;32(6):1017–1025. [PMC free article] [PubMed] [Google Scholar]
  3. Collier D. S., Thiru S., Calne R. Kidney transplantation in the dog receiving FK-506. Transplant Proc. 1987 Oct;19(5 Suppl 6):62–62. [PubMed] [Google Scholar]
  4. Dongworth D. W., Klaus G. G. Effects of cyclosporin A on the immune system of the mouse. I. Evidence for a direct selective effect of cyclosporin A on B cells responding to anti-immunoglobulin antibodies. Eur J Immunol. 1982 Dec;12(12):1018–1022. doi: 10.1002/eji.1830121207. [DOI] [PubMed] [Google Scholar]
  5. Kino T., Hatanaka H., Hashimoto M., Nishiyama M., Goto T., Okuhara M., Kohsaka M., Aoki H., Imanaka H. FK-506, a novel immunosuppressant isolated from a Streptomyces. I. Fermentation, isolation, and physico-chemical and biological characteristics. J Antibiot (Tokyo) 1987 Sep;40(9):1249–1255. doi: 10.7164/antibiotics.40.1249. [DOI] [PubMed] [Google Scholar]
  6. Kino T., Hatanaka H., Miyata S., Inamura N., Nishiyama M., Yajima T., Goto T., Okuhara M., Kohsaka M., Aoki H. FK-506, a novel immunosuppressant isolated from a Streptomyces. II. Immunosuppressive effect of FK-506 in vitro. J Antibiot (Tokyo) 1987 Sep;40(9):1256–1265. doi: 10.7164/antibiotics.40.1256. [DOI] [PubMed] [Google Scholar]
  7. Kishimoto T., Yoshizaki K., Kimoto M., Okada M., Kuritani T., Kikutani H., Shimizu K., Nakagawa T., Nakagawa N., Miki Y. B cell growth and differentiation factors and mechanism of B cell activation. Immunol Rev. 1984 Apr;78:97–118. doi: 10.1111/j.1600-065x.1984.tb00478.x. [DOI] [PubMed] [Google Scholar]
  8. Lim S. M., Thiru S., White D. J. Heterotopic heart transplantation in the rat receiving FK-506. Transplant Proc. 1987 Oct;19(5 Suppl 6):68–70. [PubMed] [Google Scholar]
  9. Muraguchi A., Butler J. L., Kehrl J. H., Falkoff R. J., Fauci A. S. Selective suppression of an early step in human B cell activation by cyclosporin A. J Exp Med. 1983 Sep 1;158(3):690–702. doi: 10.1084/jem.158.3.690. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Ochiai T., Nagata M., Nakajima K., Sakamoto K., Asano T., Isono K. Prolongation of canine renal allograft survival by treatment with FK-506. Transplant Proc. 1987 Oct;19(5 Suppl 6):53–56. [PubMed] [Google Scholar]
  11. Paavonen T., Häyry P. Effect of cyclosporin A on T-dependent and T-independent immunoglobulin synthesis in vitro. Nature. 1980 Oct 9;287(5782):542–544. doi: 10.1038/287542a0. [DOI] [PubMed] [Google Scholar]
  12. Sawada S., Suzuki G., Kawase Y., Takaku F. Novel immunosuppressive agent, FK506. In vitro effects on the cloned T cell activation. J Immunol. 1987 Sep 15;139(6):1797–1803. [PubMed] [Google Scholar]
  13. 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]
  14. Snyder D. S., Wright C. L., Ting C. Inhibition of human monocyte antigen presentation, but not HLA-DR expression, by cyclosporine. Transplantation. 1987 Sep;44(3):407–411. doi: 10.1097/00007890-198709000-00016. [DOI] [PubMed] [Google Scholar]
  15. Suzuki N., Sakane T. Mechanism of T cell-derived helper factor production upon stimulation with pokeweed mitogen in humans. Clin Exp Immunol. 1988 Feb;71(2):343–349. [PMC free article] [PubMed] [Google Scholar]
  16. Suzuki N., Sakane T., Ueda Y., Murakawa Y., Tsunematsu T. Implications for the role of cognate interactions in in vitro human B cell activation by Staphylococcus aureus Cowan I and pokeweed mitogen. J Clin Invest. 1986 Jan;77(1):294–300. doi: 10.1172/JCI112290. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Suzuki N., Ueda Y., Sakane T. Differential mechanism for differentiation into immunoglobulin-secreting cells in human resting B lymphocyte subsets isolated on the basis of cell density. J Clin Invest. 1988 Jan;81(1):261–269. doi: 10.1172/JCI113304. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Yoshimura N., Matsui S., Hamashima T., Oka T. Effect of a new immunosuppressive agent, FK506, on human lymphocyte responses in vitro. I. Inhibition of expression of alloantigen-activated suppressor cells, as well as induction of alloreactivity. Transplantation. 1989 Feb;47(2):351–356. doi: 10.1097/00007890-198902000-00034. [DOI] [PubMed] [Google Scholar]
  19. Zeevi A., Duquesnoy R., Eiras G., Rabinowich H., Todo S., Makowka L., Starzl T. E. Immunosuppressive effect of FK-506 on in vitro lymphocyte alloactivation: synergism with cyclosporine A. Transplant Proc. 1987 Oct;19(5 Suppl 6):40–44. [PMC free article] [PubMed] [Google Scholar]

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