Skip to main content
PMC home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1992 Jan 1;175(1):15–21. doi: 10.1084/jem.175.1.15

Antigen-pulsed dendritic cells can efficiently induce an antibody response in vivo

PMCID: PMC2119067  PMID: 1370527

Abstract

The aim of this study was to develop an immunization procedure avoiding external adjuvant. Data are presented showing that syngeneic dendritic cells (DC), which have been pulsed in vitro with antigen, induce a strong antibody response in mice. By contrast, antigen (Ag)-pulsed low- density B cells, although equally able to induce interleukin 2 secretion by an Ag-specific T cell hybridoma in vitro, only weakly prime the mice in vivo. Moreover, we show that the injection of Ag- pulsed DC induces the synthesis of isotypes similar to the immunoglobulin classes detected after immunization with the same Ag in complete Freund's adjuvant. Importantly, high amounts of IgG2a antibodies are produced, suggesting that T helper type 1 cells are activated. Collectively, these data indicate that DC can initiate a primary humoral response and that they may be used as physiological adjuvant in vivo.

Full Text

The Full Text of this article is available as a PDF (581.2 KB).

Selected References

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

  1. Aiba S., Katz S. I. Phenotypic and functional characteristics of in vivo-activated Langerhans cells. J Immunol. 1990 Nov 1;145(9):2791–2796. [PubMed] [Google Scholar]
  2. Austyn J. M., Kupiec-Weglinski J. W., Hankins D. F., Morris P. J. Migration patterns of dendritic cells in the mouse. Homing to T cell-dependent areas of spleen, and binding within marginal zone. J Exp Med. 1988 Feb 1;167(2):646–651. doi: 10.1084/jem.167.2.646. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Britz J. S., Askenase P. W., Ptak W., Steinman R. M., Gershon R. K. Specialized antigen-presenting cells. Splenic dendritic cells and peritoneal-exudate cells induced by mycobacteria activate effector T cells that are resistant to suppression. J Exp Med. 1982 May 1;155(5):1344–1356. doi: 10.1084/jem.155.5.1344. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Crowley M., Inaba K., Steinman R. M. Dendritic cells are the principal cells in mouse spleen bearing immunogenic fragments of foreign proteins. J Exp Med. 1990 Jul 1;172(1):383–386. doi: 10.1084/jem.172.1.383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Crowley M., Inaba K., Witmer-Pack M., Steinman R. M. The cell surface of mouse dendritic cells: FACS analyses of dendritic cells from different tissues including thymus. Cell Immunol. 1989 Jan;118(1):108–125. doi: 10.1016/0008-8749(89)90361-4. [DOI] [PubMed] [Google Scholar]
  6. Faustman D. L., Steinman R. M., Gebel H. M., Hauptfeld V., Davie J. M., Lacy P. E. Prevention of rejection of murine islet allografts by pretreatment with anti-dendritic cell antibody. Proc Natl Acad Sci U S A. 1984 Jun;81(12):3864–3868. doi: 10.1073/pnas.81.12.3864. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fossum S. Lymph-borne dendritic leucocytes do not recirculate, but enter the lymph node paracortex to become interdigitating cells. Scand J Immunol. 1988 Jan;27(1):97–105. doi: 10.1111/j.1365-3083.1988.tb02326.x. [DOI] [PubMed] [Google Scholar]
  8. Fox B. S., Quill H., Carlson L., Schwartz R. H. Quantitative analysis of the T cell response to antigen and planar membranes containing purified Ia molecules. J Immunol. 1987 May 15;138(10):3367–3374. [PubMed] [Google Scholar]
  9. Francotte M., Urbain J. Enhancement of antibody response by mouse dendritic cells pulsed with tobacco mosaic virus or with rabbit antiidiotypic antibodies raised against a private rabbit idiotype. Proc Natl Acad Sci U S A. 1985 Dec;82(23):8149–8152. doi: 10.1073/pnas.82.23.8149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Freeman G. J., Gray G. S., Gimmi C. D., Lombard D. B., Zhou L. J., White M., Fingeroth J. D., Gribben J. G., Nadler L. M. Structure, expression, and T cell costimulatory activity of the murine homologue of the human B lymphocyte activation antigen B7. J Exp Med. 1991 Sep 1;174(3):625–631. doi: 10.1084/jem.174.3.625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gajewski T. F., Pinnas M., Wong T., Fitch F. W. Murine Th1 and Th2 clones proliferate optimally in response to distinct antigen-presenting cell populations. J Immunol. 1991 Mar 15;146(6):1750–1758. [PubMed] [Google Scholar]
  12. Inaba K., Metlay J. P., Crowley M. T., Steinman R. M. Dendritic cells pulsed with protein antigens in vitro can prime antigen-specific, MHC-restricted T cells in situ. J Exp Med. 1990 Aug 1;172(2):631–640. doi: 10.1084/jem.172.2.631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Inaba K., Steinman R. M. Resting and sensitized T lymphocytes exhibit distinct stimulatory (antigen-presenting cell) requirements for growth and lymphokine release. J Exp Med. 1984 Dec 1;160(6):1717–1735. doi: 10.1084/jem.160.6.1717. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Inaba K., Steinman R. M., Van Voorhis W. C., Muramatsu S. Dendritic cells are critical accessory cells for thymus-dependent antibody responses in mouse and in man. Proc Natl Acad Sci U S A. 1983 Oct;80(19):6041–6045. doi: 10.1073/pnas.80.19.6041. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Inaba K., Witmer M. D., Steinman R. M. Clustering of dendritic cells, helper T lymphocytes, and histocompatible B cells during primary antibody responses in vitro. J Exp Med. 1984 Sep 1;160(3):858–876. doi: 10.1084/jem.160.3.858. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Janeway C. A., Jr, Ron J., Katz M. E. The B cell is the initiating antigen-presenting cell in peripheral lymph nodes. J Immunol. 1987 Feb 15;138(4):1051–1055. [PubMed] [Google Scholar]
  17. Kaminski M. S., Kitamura K., Maloney D. G., Campbell M. J., Levy R. Importance of antibody isotype in monoclonal anti-idiotype therapy of a murine B cell lymphoma. A study of hybridoma class switch variants. J Immunol. 1986 Feb 1;136(3):1123–1130. [PubMed] [Google Scholar]
  18. Karagouni E. E., Hadjipetrou-Kourounakis L. Regulation of isotype immunoglobulin production by adjuvants in vivo. Scand J Immunol. 1990 Jun;31(6):745–754. doi: 10.1111/j.1365-3083.1990.tb02826.x. [DOI] [PubMed] [Google Scholar]
  19. Koide S., Steinman R. M. Induction of murine interleukin 1: stimuli and responsive primary cells. Proc Natl Acad Sci U S A. 1987 Jun;84(11):3802–3806. doi: 10.1073/pnas.84.11.3802. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kurt-Jones E. A., Liano D., HayGlass K. A., Benacerraf B., Sy M. S., Abbas A. K. The role of antigen-presenting B cells in T cell priming in vivo. Studies of B cell-deficient mice. J Immunol. 1988 Jun 1;140(11):3773–3778. [PubMed] [Google Scholar]
  21. Kämpgen E., Koch N., Koch F., Stöger P., Heufler C., Schuler G., Romani N. Class II major histocompatibility complex molecules of murine dendritic cells: synthesis, sialylation of invariant chain, and antigen processing capacity are down-regulated upon culture. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3014–3018. doi: 10.1073/pnas.88.8.3014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Larsen C. P., Steinman R. M., Witmer-Pack M., Hankins D. F., Morris P. J., Austyn J. M. Migration and maturation of Langerhans cells in skin transplants and explants. J Exp Med. 1990 Nov 1;172(5):1483–1493. doi: 10.1084/jem.172.5.1483. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lassila O., Vainio O., Matzinger P. Can B cells turn on virgin T cells? Nature. 1988 Jul 21;334(6179):253–255. doi: 10.1038/334253a0. [DOI] [PubMed] [Google Scholar]
  24. Lechler R. I., Batchelor J. R. Restoration of immunogenicity to passenger cell-depleted kidney allografts by the addition of donor strain dendritic cells. J Exp Med. 1982 Jan 1;155(1):31–41. doi: 10.1084/jem.155.1.31. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Macatonia S. E., Knight S. C., Edwards A. J., Griffiths S., Fryer P. Localization of antigen on lymph node dendritic cells after exposure to the contact sensitizer fluorescein isothiocyanate. Functional and morphological studies. J Exp Med. 1987 Dec 1;166(6):1654–1667. doi: 10.1084/jem.166.6.1654. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Mosmann T. R., Coffman R. L. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol. 1989;7:145–173. doi: 10.1146/annurev.iy.07.040189.001045. [DOI] [PubMed] [Google Scholar]
  27. Müller W., Vandenabeele P. A T cell clone which responds to interleukin 2 but not to interleukin 4. Eur J Immunol. 1987 Apr;17(4):579–580. doi: 10.1002/eji.1830170424. [DOI] [PubMed] [Google Scholar]
  28. Puré E., Inaba K., Crowley M. T., Tardelli L., Witmer-Pack M. D., Ruberti G., Fathman G., Steinman R. M. Antigen processing by epidermal Langerhans cells correlates with the level of biosynthesis of major histocompatibility complex class II molecules and expression of invariant chain. J Exp Med. 1990 Nov 1;172(5):1459–1469. doi: 10.1084/jem.172.5.1459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Romani N., Koide S., Crowley M., Witmer-Pack M., Livingstone A. M., Fathman C. G., Inaba K., Steinman R. M. Presentation of exogenous protein antigens by dendritic cells to T cell clones. Intact protein is presented best by immature, epidermal Langerhans cells. J Exp Med. 1989 Mar 1;169(3):1169–1178. doi: 10.1084/jem.169.3.1169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Ron Y., Sprent J. T cell priming in vivo: a major role for B cells in presenting antigen to T cells in lymph nodes. J Immunol. 1987 May 1;138(9):2848–2856. [PubMed] [Google Scholar]
  31. Snapper C. M., Paul W. E. Interferon-gamma and B cell stimulatory factor-1 reciprocally regulate Ig isotype production. Science. 1987 May 22;236(4804):944–947. doi: 10.1126/science.3107127. [DOI] [PubMed] [Google Scholar]
  32. Steinman R. M. The dendritic cell system and its role in immunogenicity. Annu Rev Immunol. 1991;9:271–296. doi: 10.1146/annurev.iy.09.040191.001415. [DOI] [PubMed] [Google Scholar]
  33. Weaver C. T., Hawrylowicz C. M., Unanue E. R. T helper cell subsets require the expression of distinct costimulatory signals by antigen-presenting cells. Proc Natl Acad Sci U S A. 1988 Nov;85(21):8181–8185. doi: 10.1073/pnas.85.21.8181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Wilbanks G. A., Streilein J. W. Distinctive humoral immune responses following anterior chamber and intravenous administration of soluble antigen. Evidence for active suppression of IgG2-secreting B lymphocytes. Immunology. 1990 Dec;71(4):566–572. [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES