Skip to main content
PMC home page
Immunology logoLink to Immunology
. 1992 Mar;75(3):493–498.

Involvement of antigen-presenting cells in the enhancement of the in vitro antibody responses by cholera toxin B subunit.

Y Hirabayashi 1, S I Tamura 1, K Shimada 1, T Kurata 1
PMCID: PMC1384745  PMID: 1374056

Abstract

The enhancing effect of cholera toxin B subunit (CTB) on primary antibody responses to keyhole limpet haemocyanin (KLH) and the cellular basis of the effect were investigated, using in vitro cultures of mouse spleen cells. CTB (1-100 ng/ml) enhanced anti-KLH IgM, IgG and IgA antibody responses in a dose-dependent manner, when added to the cultures with KLH. This immunoenhancement was antigen specific, but not due to either polyclonal activation of the spleen cells or antigenic cross-reactivity between CTB and KLH. CTB did not affect the kinetics of the anti-KLH antibody responses. Early (Days 0-1) addition of CTB to the cultures enhanced the anti-KLH antibody production, whereas late (Days 5-7) addition of CTB did not. Addition of CTB with KLH to splenic adherent cells (SAC) resulted in a dose-dependent enhancement of the anti-KLH antibody responses, when the SAC were reconstituted with unimmunized non-adherent cells. Moreover, CTB enhanced IL-1 secretion from SAC incubated with KLH. These results suggest that CTB enhances the primary anti-KLH antibody responses in vitro by acting on early events in the responses, and that antigen-presenting cells play a major role in the enhancement.

Full text

PDF
494

Selected References

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

  1. Bromander A., Holmgren J., Lycke N. Cholera toxin stimulates IL-1 production and enhances antigen presentation by macrophages in vitro. J Immunol. 1991 May 1;146(9):2908–2914. [PubMed] [Google Scholar]
  2. Burchiel S. W., Melmon K. L. Augmentation of the in vitro humoral immune response by pharmacologic agents. I: An explanation for the differential enhancement of humoral immunity via agents that elevate cAMP. Immunopharmacology. 1979 Mar;1(2):137–150. doi: 10.1016/0162-3109(79)90050-x. [DOI] [PubMed] [Google Scholar]
  3. Chen K. S., Strober W. Cholera holotoxin and its B subunit enhance Peyer's patch B cell responses induced by orally administered influenza virus: disproportionate cholera toxin enhancement of the IgA B cell response. Eur J Immunol. 1990 Feb;20(2):433–436. doi: 10.1002/eji.1830200230. [DOI] [PubMed] [Google Scholar]
  4. Clarke C. J., Wilson A. D., Williams N. A., Stokes C. R. Mucosal priming of T-lymphocyte responses to fed protein antigens using cholera toxin as an adjuvant. Immunology. 1991 Mar;72(3):323–328. [PMC free article] [PubMed] [Google Scholar]
  5. Cook R. G., Stavitsky A. B., Schoenberg M. D. Regulation of the in vitro early anamnestic antibody response by exogenous cholera enterotoxin and cyclic AMP. J Immunol. 1975 Jan;114(1 Pt 2):426–434. [PubMed] [Google Scholar]
  6. Denizot F., Lang R. Rapid colorimetric assay for cell growth and survival. Modifications to the tetrazolium dye procedure giving improved sensitivity and reliability. J Immunol Methods. 1986 May 22;89(2):271–277. doi: 10.1016/0022-1759(86)90368-6. [DOI] [PubMed] [Google Scholar]
  7. Elson C. O., Ealding W. Generalized systemic and mucosal immunity in mice after mucosal stimulation with cholera toxin. J Immunol. 1984 Jun;132(6):2736–2741. [PubMed] [Google Scholar]
  8. Elson C. O., Ealding W., Lefkowitz J. A lavage technique allowing repeated measurement of IgA antibody in mouse intestinal secretions. J Immunol Methods. 1984 Feb 24;67(1):101–108. doi: 10.1016/0022-1759(84)90089-9. [DOI] [PubMed] [Google Scholar]
  9. Gillis S., Mizel S. B. T-Cell lymphoma model for the analysis of interleukin 1-mediated T-cell activation. Proc Natl Acad Sci U S A. 1981 Feb;78(2):1133–1137. doi: 10.1073/pnas.78.2.1133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hirabayashi Y., Kurata H., Funato H., Nagamine T., Aizawa C., Tamura S., Shimada K., Kurata T. Comparison of intranasal inoculation of influenza HA vaccine combined with cholera toxin B subunit with oral or parenteral vaccination. Vaccine. 1990 Jun;8(3):243–248. doi: 10.1016/0264-410x(90)90053-o. [DOI] [PubMed] [Google Scholar]
  11. Hirabayashi Y., Tamura S. I., Suzuki Y., Nagamine T., Aizawa C., Shimada K., Kurata T. H-2-unrestricted adjuvant effect of cholera toxin B subunit on murine antibody responses to influenza virus haemagglutinin. Immunology. 1991 Mar;72(3):329–335. [PMC free article] [PubMed] [Google Scholar]
  12. Hodes R. J., Singer A. Cellular and genetic control of antibody responses in vitro. I. Cellular requirements for the generation of genetically controlled primary IgM responses to soluble antigens. Eur J Immunol. 1977 Dec;7(12):892–897. doi: 10.1002/eji.1830071214. [DOI] [PubMed] [Google Scholar]
  13. Holmgren J. Actions of cholera toxin and the prevention and treatment of cholera. Nature. 1981 Jul 30;292(5822):413–417. doi: 10.1038/292413a0. [DOI] [PubMed] [Google Scholar]
  14. Ishizuka M., Braun W., Matsumoto T. Cyclic AMP and immune responses. I. Influence of poly A:U and cAMP on antibody formation in vitro. J Immunol. 1971 Oct;107(4):1027–1035. [PubMed] [Google Scholar]
  15. Kumagai K., Itoh K., Hinuma S., Tada M. Pretreatment of plastic Petri dishes with fetal calf serum. A simple method for macrophage isolation. J Immunol Methods. 1979;29(1):17–25. doi: 10.1016/0022-1759(79)90121-2. [DOI] [PubMed] [Google Scholar]
  16. Lycke N., Holmgren J. Strong adjuvant properties of cholera toxin on gut mucosal immune responses to orally presented antigens. Immunology. 1986 Oct;59(2):301–308. [PMC free article] [PubMed] [Google Scholar]
  17. McKenzie S. J., Halsey J. F. Cholera toxin B subunit as a carrier protein to stimulate a mucosal immune response. J Immunol. 1984 Oct;133(4):1818–1824. [PubMed] [Google Scholar]
  18. Moss J., Burns D. L., Hsia J. A., Hewlett E. L., Guerrant R. L., Vaughan M. NIH conference. Cyclic nucleotides: mediators of bacterial toxin action in disease. Ann Intern Med. 1984 Nov;101(5):653–666. doi: 10.7326/0003-4819-101-5-653. [DOI] [PubMed] [Google Scholar]
  19. Northrup R. S., Fauci A. S. Adjuvant effect of cholera enterotoxin on the immune response of the mouse to sheep red blood cells. J Infect Dis. 1972 Jun;125(6):672–673. doi: 10.1093/infdis/125.6.672. [DOI] [PubMed] [Google Scholar]
  20. Tamura S. I., Samegai Y., Kurata H., Kikuta K., Nagamine T., Aizawa C., Kurata T. Enhancement of protective antibody responses by cholera toxin B subunit inoculated intranasally with influenza vaccine. Vaccine. 1989 Jun;7(3):257–262. doi: 10.1016/0264-410x(89)90240-5. [DOI] [PubMed] [Google Scholar]
  21. Tamura S., Samegai Y., Kurata H., Nagamine T., Aizawa C., Kurata T. Protection against influenza virus infection by vaccine inoculated intranasally with cholera toxin B subunit. Vaccine. 1988 Oct;6(5):409–413. doi: 10.1016/0264-410x(88)90140-5. [DOI] [PubMed] [Google Scholar]
  22. Teh H. S., Paetkau V. Biphasic effect of cyclic AMP on an immune response. Nature. 1974 Aug 9;250(5466):505–507. doi: 10.1038/250505a0. [DOI] [PubMed] [Google Scholar]
  23. Wilson A. D., Clarke C. J., Stokes C. R. Whole cholera toxin and B subunit act synergistically as an adjuvant for the mucosal immune response of mice to keyhole limpet haemocyanin. Scand J Immunol. 1990 Apr;31(4):443–451. doi: 10.1111/j.1365-3083.1990.tb02791.x. [DOI] [PubMed] [Google Scholar]
  24. Wilson A. D., Stokes C. R., Bourne F. J. Adjuvant effect of cholera toxin on the mucosal immune response to soluble proteins. Differences between mouse strains and protein antigens. Scand J Immunol. 1989 Jun;29(6):739–745. [PubMed] [Google Scholar]
  25. Woogen S. D., Ealding W., Elson C. O. Inhibition of murine lymphocyte proliferation by the B subunit of cholera toxin. J Immunol. 1987 Dec 1;139(11):3764–3770. [PubMed] [Google Scholar]
  26. van Heyningen S. Cholera toxin. Biosci Rep. 1982 Mar;2(3):135–146. doi: 10.1007/BF01116376. [DOI] [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES