Skip to main content
NCBI home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1992 Sep;89(3):369–373. doi: 10.1111/j.1365-2249.1992.tb06964.x

Impaired proliferative responses of peripheral blood B cells from splenectomized subjects to phorbol ester and ionophore.

P N Foster 1, L K Trejdosiewicz 1
PMCID: PMC1554479  PMID: 1325305

Abstract

The responses of peripheral blood B cells to mitogenic stimulation were examined in 12 splenectomized subjects without residual splenic function, as determined by pitted erythrocyte counts. These were compared to a group of healthy controls matched for age and sex. Polyclonal anti-immunoglobulin evoked a normal transient elevation in intracellular free Ca2+ in splenectomized subjects, thereby suggesting that the early events of the signal transduction pathway are not impaired. However, mitogenic stimulation by pre-treatment with phorbol ester and culture in presence of a calcium ionophore (Ionomycin) resulted in reduced uptake of 3H-thymidine and subsequent proliferation. Nevertheless, entry into the mitotic cycle, as assessed by expression of Ki67, was slightly, but not significantly impaired. Unlike in normal controls, where up to 7% of freshly-isolated B cells were Ki67+, almost no Ki67+ peripheral B cells were observed in splenectomized subjects. The data are consistent with the hypothesis that peripheral B cells in splenectomized subjects are in a reduced state of activation compared with normal controls and require additional growth factor stimulation before they can undergo mitosis.

Full text

PDF
369

Selected References

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

  1. Aaberge I. S., Heier H. E., Hem E., Giercksky K. E., Groeng E. C. IgM and IgG response to pneumococcal polysaccharide vaccine in normal individuals and individuals splenectomized due to trauma. Acta Pathol Microbiol Immunol Scand C. 1984 Feb;92(1):11–16. doi: 10.1111/j.1699-0463.1984.tb00046.x. [DOI] [PubMed] [Google Scholar]
  2. Amlot P. L., Hayes A. E. Impaired human antibody response to the thymus-independent antigen, DNP-Ficoll, after splenectomy. Implications for post-splenectomy infections. Lancet. 1985 May 4;1(8436):1008–1011. doi: 10.1016/s0140-6736(85)91613-7. [DOI] [PubMed] [Google Scholar]
  3. Andersen V., Cohn J., Sorensen S. F. Immunological studies in children before and after splenectomy. Acta Paediatr Scand. 1976 Jul;65(4):409–415. doi: 10.1111/j.1651-2227.1976.tb04907.x. [DOI] [PubMed] [Google Scholar]
  4. Cambier J. C., Justement L. B., Newell M. K., Chen Z. Z., Harris L. K., Sandoval V. M., Klemsz M. J., Ransom J. T. Transmembrane signals and intracellular "second messengers" in the regulation of quiescent B-lymphocyte activation. Immunol Rev. 1987 Feb;95:37–57. doi: 10.1111/j.1600-065x.1987.tb00499.x. [DOI] [PubMed] [Google Scholar]
  5. Corazza G. R., Bullen A. W., Hall R., Robinson P. J., Losowsky M. S. Simple method of assessing splenic function in coeliac disease. Clin Sci (Lond) 1981 Jan;60(1):109–113. doi: 10.1042/cs0600109. [DOI] [PubMed] [Google Scholar]
  6. Corazza G. R., Tarozzi C., Vaira D., Frisoni M., Gasbarrini G. Return of splenic function after splenectomy: how much tissue is needed? Br Med J (Clin Res Ed) 1984 Oct 6;289(6449):861–864. doi: 10.1136/bmj.289.6449.861. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Di Padova F., Dürig M., Harder F., Di Padova C., Zanussi C. Impaired antipneumococcal antibody production in patients without spleens. Br Med J (Clin Res Ed) 1985 Jan 5;290(6461):14–16. doi: 10.1136/bmj.290.6461.14. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Drew P. A., Kiroff G. K., Ferrante A., Cohen R. C. Alterations in immunoglobulin synthesis by peripheral blood mononuclear cells from splenectomized patients with and without splenic regrowth. J Immunol. 1984 Jan;132(1):191–196. [PubMed] [Google Scholar]
  9. Gerdes J., Lemke H., Baisch H., Wacker H. H., Schwab U., Stein H. Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol. 1984 Oct;133(4):1710–1715. [PubMed] [Google Scholar]
  10. Grynkiewicz G., Poenie M., Tsien R. Y. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem. 1985 Mar 25;260(6):3440–3450. [PubMed] [Google Scholar]
  11. Guy G. R., Bunce C. M., Gordon J., Michell R. H., Brown G. A combination of calcium ionophore and 12-O-tetradecanoyl-phorbol-13-acetate (TPA) stimulates the growth of purified resting B cells. Scand J Immunol. 1985 Nov;22(5):591–596. doi: 10.1111/j.1365-3083.1985.tb01919.x. [DOI] [PubMed] [Google Scholar]
  12. Hosea S. W., Burch C. G., Brown E. J., Berg R. A., Frank M. M. Impaired immune response of splenectomised patients to polyvalent pneumococcal vaccine. Lancet. 1981 Apr 11;1(8224):804–807. doi: 10.1016/s0140-6736(81)92681-7. [DOI] [PubMed] [Google Scholar]
  13. Inglés J., Engel P., De La Calle O., Gallart T. Differential responsiveness of human B lymphocytes to phorbol ester and calcium ionophore based on their state of activation. Immunology. 1989 Jul;67(3):359–364. [PMC free article] [PubMed] [Google Scholar]
  14. Jelinek D. F., Lipsky P. E. Regulation of human B lymphocyte activation, proliferation, and differentiation. Adv Immunol. 1987;40:1–59. doi: 10.1016/s0065-2776(08)60237-0. [DOI] [PubMed] [Google Scholar]
  15. Kiroff G. K., Hodgen A. N., Drew P. A., Jamieson G. G. Lack of effect of splenic regrowth on the reduced antibody responses to pneumococcal polysaccharides in splenectomized patients. Clin Exp Immunol. 1985 Oct;62(1):48–56. [PMC free article] [PubMed] [Google Scholar]
  16. Lanng Nielsen J., Tauris P., Johnsen H. E., Ellegaard J. The cellular immune response after splenectomy in humans. Impaired immunoglobulin synthesis in vitro. Scand J Haematol. 1983 Jul;31(1):85–95. doi: 10.1111/j.1600-0609.1983.tb02141.x. [DOI] [PubMed] [Google Scholar]
  17. Müller C., Mannhalter J. W., Ahmad R., Zlabinger G., Wurnig P., Eibl M. M. Peripheral blood mononuclear cells of splenectomized patients are unable to differentiate into immunoglobulin-secreting cells after pokeweed mitogen stimulation. Clin Immunol Immunopathol. 1984 Apr;31(1):118–123. doi: 10.1016/0090-1229(84)90196-x. [DOI] [PubMed] [Google Scholar]
  18. Naylor J. R., James S. R., Trejdosiewicz L. K. Intracellular free Ca2+ fluxes and responses to phorbol ester in T lymphocytes from healthy elderly subjects. Clin Exp Immunol. 1992 Jul;89(1):158–163. doi: 10.1111/j.1365-2249.1992.tb06896.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Pozzan T., Arslan P., Tsien R. Y., Rink T. J. Anti-immunoglobulin, cytoplasmic free calcium, and capping in B lymphocytes. J Cell Biol. 1982 Aug;94(2):335–340. doi: 10.1083/jcb.94.2.335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Ralph P., Kishimoto T. Tumor promoter phorbol myristic acetate is a T-cell dependent inducer of immunoglobulin secretion in human lymphocytes. Clin Immunol Immunopathol. 1982 Mar;22(3):340–348. doi: 10.1016/0090-1229(82)90051-4. [DOI] [PubMed] [Google Scholar]
  21. Sieber G., Breyer H. G., Herrmann F., Rühl H. Abnormalities of B-cell activation and immunoregulation in splenectomized patients. Immunobiology. 1985 Apr;169(3):263–271. doi: 10.1016/s0171-2985(85)80038-3. [DOI] [PubMed] [Google Scholar]
  22. Tauris P., Nielsen J. L. Irradiated autologous T cells restore the in vitro responsiveness of PWM-activated peripheral blood lymphocytes from splenectomized individuals. Acta Pathol Microbiol Immunol Scand C. 1983 Aug;91(4):257–261. [PubMed] [Google Scholar]
  23. Thompson C. B., Scher I., Schaefer M. E., Lindsten T., Finkelman F. D., Mond J. J. Size-dependent B lymphocyte subpopulations: relationship of cell volume to surface phenotype, cell cycle, proliferative response, and requirements for antibody production to TNP-Ficoll and TNP-BA. J Immunol. 1984 Nov;133(5):2333–2342. [PubMed] [Google Scholar]
  24. Treves S., Di Virgilio F., Cerundolo V., Zanovello P., Collavo D., Pozzan T. Calcium and inositolphosphates in the activation of T cell-mediated cytotoxicity. J Exp Med. 1987 Jul 1;166(1):33–42. doi: 10.1084/jem.166.1.33. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Tsien R. Y., Pozzan T., Rink T. J. Calcium homeostasis in intact lymphocytes: cytoplasmic free calcium monitored with a new, intracellularly trapped fluorescent indicator. J Cell Biol. 1982 Aug;94(2):325–334. doi: 10.1083/jcb.94.2.325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Walker L., Guy G., Brown G., Rowe M., Milner A. E., Gordon J. Control of human B-lymphocyte replication. I. Characterization of novel activation states that precede the entry of G0 B cells into cycle. Immunology. 1986 Aug;58(4):583–589. [PMC free article] [PubMed] [Google Scholar]
  27. Wang W. C., Herrod H. G., Valenski W. R., Wyatt R. J. Lymphocyte and complement abnormalities in splenectomized patients with hematologic disorders. Am J Hematol. 1988 Aug;28(4):239–245. doi: 10.1002/ajh.2830280406. [DOI] [PubMed] [Google Scholar]
  28. Westerhausen M., Wörsdörfer O., Gessner U., De Giuli R., Senn H. J. Immunological changes following posttraumatic splenectomy. Blut. 1981 Dec;43(6):345–353. doi: 10.1007/BF00320312. [DOI] [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES