Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1996 Mar 1;183(3):751–757. doi: 10.1084/jem.183.3.751

Dendritic cells but not B cells present antigenic complexes to class II- restricted T cells after administration of protein in adjuvant

PMCID: PMC2192345  PMID: 8642279

Abstract

We have analyzed the relative contribution of dendritic cells (DC) and B cells in the presentation of peptide-class II complexes in an inflammatory situation in vivo. Draining lymph node cells from mice immunized subcutaneously with hen egg-white lysozyme (HEL) in adjuvant display HEL peptide-major histocompatibility complex class II complexes able to stimulate, in the absence of any further antigen addition, specific T hybridoma cells. The antigen-presenting capacity of three different antigen-presenting cell (APC) populations recruited in lymph nodes, DC (N418+, class II+, B220-, low buoyant density), large B cells (B220+, low buoyant density), and small B cells (B220+, high buoyant density), was analyzed. After immunization with HEL in adjuvant, DC are the only lymph node APC population expressing detectable HEL peptide- class II complexes. These results indicate that lymph node DC and not B cells are the APC initiating the immune response in vivo after administration of antigen in adjuvant.

Full Text

The Full Text of this article is available as a PDF (718.2 KB).

Selected References

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

  1. Adorini L., Guéry J. C., Fuchs S., Ortiz-Navarrete V., Hämmerling G. J., Momburg F. Processing of endogenously synthesized hen egg-white lysozyme retained in the endoplasmic reticulum or in secretory form gives rise to a similar but not identical set of epitopes recognized by class II-restricted T cells. J Immunol. 1993 Oct 1;151(7):3576–3586. [PubMed] [Google Scholar]
  2. Adorini L., Sette A., Buus S., Grey H. M., Darsley M., Lehmann P. V., Doria G., Nagy Z. A., Appella E. Interaction of an immunodominant epitope with Ia molecules in T-cell activation. Proc Natl Acad Sci U S A. 1988 Jul;85(14):5181–5185. doi: 10.1073/pnas.85.14.5181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Agger R., Crowley M. T., Witmer-Pack M. D. The surface of dendritic cells in the mouse as studied with monoclonal antibodies. Int Rev Immunol. 1990;6(2-3):89–101. doi: 10.3109/08830189009056621. [DOI] [PubMed] [Google Scholar]
  4. Bhardwaj N., Friedman S. M., Cole B. C., Nisanian A. J. Dendritic cells are potent antigen-presenting cells for microbial superantigens. J Exp Med. 1992 Jan 1;175(1):267–273. doi: 10.1084/jem.175.1.267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bhardwaj N., Young J. W., Nisanian A. J., Baggers J., Steinman R. M. Small amounts of superantigen, when presented on dendritic cells, are sufficient to initiate T cell responses. J Exp Med. 1993 Aug 1;178(2):633–642. doi: 10.1084/jem.178.2.633. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Croft M., Duncan D. D., Swain S. L. Response of naive antigen-specific CD4+ T cells in vitro: characteristics and antigen-presenting cell requirements. J Exp Med. 1992 Nov 1;176(5):1431–1437. doi: 10.1084/jem.176.5.1431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Crowley M. T., Inaba K., Witmer-Pack M. D., Gezelter S., Steinman R. M. Use of the fluorescence activated cell sorter to enrich dendritic cells from mouse spleen. J Immunol Methods. 1990 Oct 4;133(1):55–66. doi: 10.1016/0022-1759(90)90318-p. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Epstein M. M., Di Rosa F., Jankovic D., Sher A., Matzinger P. Successful T cell priming in B cell-deficient mice. J Exp Med. 1995 Oct 1;182(4):915–922. doi: 10.1084/jem.182.4.915. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Eynon E. E., Parker D. C. Small B cells as antigen-presenting cells in the induction of tolerance to soluble protein antigens. J Exp Med. 1992 Jan 1;175(1):131–138. doi: 10.1084/jem.175.1.131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fuchs E. J., Matzinger P. B cells turn off virgin but not memory T cells. Science. 1992 Nov 13;258(5085):1156–1159. doi: 10.1126/science.1439825. [DOI] [PubMed] [Google Scholar]
  12. Germain R. N., Margulies D. H. The biochemistry and cell biology of antigen processing and presentation. Annu Rev Immunol. 1993;11:403–450. doi: 10.1146/annurev.iy.11.040193.002155. [DOI] [PubMed] [Google Scholar]
  13. Goldman M., Druet P., Gleichmann E. TH2 cells in systemic autoimmunity: insights from allogeneic diseases and chemically-induced autoimmunity. Immunol Today. 1991 Jul;12(7):223–227. doi: 10.1016/0167-5699(91)90034-Q. [DOI] [PubMed] [Google Scholar]
  14. Guery J. C., Galbiati F., Smiroldo S., Adorini L. Selective development of T helper (Th)2 cells induced by continuous administration of low dose soluble proteins to normal and beta(2)-microglobulin-deficient BALB/c mice. J Exp Med. 1996 Feb 1;183(2):485–497. doi: 10.1084/jem.183.2.485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Guéry J. C., Adorini L. Dendritic cells are the most efficient in presenting endogenous naturally processed self-epitopes to class II-restricted T cells. J Immunol. 1995 Jan 15;154(2):536–544. [PubMed] [Google Scholar]
  16. Guéry J. C., Neagu M., Rodriguez-Tarduchy G., Adorini L. Selective immunosuppression by administration of major histocompatibility complex class II-binding peptides. II. Preventive inhibition of primary and secondary in vivo antibody responses. J Exp Med. 1993 May 1;177(5):1461–1468. doi: 10.1084/jem.177.5.1461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Guéry J. C., Sette A., Appella E., Adorini L. Constitutive presentation of dominant epitopes from endogenous naturally processed self-beta 2-microglobulin to class II-restricted T cells leads to self-tolerance. J Immunol. 1995 Jan 15;154(2):545–554. [PubMed] [Google Scholar]
  18. Guéry J. C., Sette A., Leighton J., Dragomir A., Adorini L. Selective immunosuppression by administration of major histocompatibility complex (MHC) class II-binding peptides. I. Evidence for in vivo MHC blockade preventing T cell activation. J Exp Med. 1992 May 1;175(5):1345–1352. doi: 10.1084/jem.175.5.1345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Ibrahim M. A., Chain B. M., Katz D. R. The injured cell: the role of the dendritic cell system as a sentinel receptor pathway. Immunol Today. 1995 Apr;16(4):181–186. doi: 10.1016/0167-5699(95)80118-9. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. 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]
  22. 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]
  23. Larsen C. P., Ritchie S. C., Pearson T. C., Linsley P. S., Lowry R. P. Functional expression of the costimulatory molecule, B7/BB1, on murine dendritic cell populations. J Exp Med. 1992 Oct 1;176(4):1215–1220. doi: 10.1084/jem.176.4.1215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. 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]
  25. Macatonia S. E., Hosken N. A., Litton M., Vieira P., Hsieh C. S., Culpepper J. A., Wysocka M., Trinchieri G., Murphy K. M., O'Garra A. Dendritic cells produce IL-12 and direct the development of Th1 cells from naive CD4+ T cells. J Immunol. 1995 May 15;154(10):5071–5079. [PubMed] [Google Scholar]
  26. Mamula M. J., Janeway C. A., Jr Do B cells drive the diversification of immune responses? Immunol Today. 1993 Apr;14(4):151–154. doi: 10.1016/0167-5699(93)90274-O. [DOI] [PubMed] [Google Scholar]
  27. Metlay J. P., Witmer-Pack M. D., Agger R., Crowley M. T., Lawless D., Steinman R. M. The distinct leukocyte integrins of mouse spleen dendritic cells as identified with new hamster monoclonal antibodies. J Exp Med. 1990 May 1;171(5):1753–1771. doi: 10.1084/jem.171.5.1753. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Romani N., Schuler G. The immunologic properties of epidermal Langerhans cells as a part of the dendritic cell system. Springer Semin Immunopathol. 1992;13(3-4):265–279. doi: 10.1007/BF00200527. [DOI] [PubMed] [Google Scholar]
  29. Ron Y., De Baetselier P., Gordon J., Feldman M., Segal S. Defective induction of antigen-reactive proliferating T cells in B cell-deprived mice. Eur J Immunol. 1981 Dec;11(12):964–968. doi: 10.1002/eji.1830111203. [DOI] [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. Ronchese F., Hausmann B. B lymphocytes in vivo fail to prime naive T cells but can stimulate antigen-experienced T lymphocytes. J Exp Med. 1993 Mar 1;177(3):679–690. doi: 10.1084/jem.177.3.679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Sallusto F., Lanzavecchia A. Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha. J Exp Med. 1994 Apr 1;179(4):1109–1118. doi: 10.1084/jem.179.4.1109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. 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]
  34. Trembleau S., Penna G., Bosi E., Mortara A., Gately M. K., Adorini L. Interleukin 12 administration induces T helper type 1 cells and accelerates autoimmune diabetes in NOD mice. J Exp Med. 1995 Feb 1;181(2):817–821. doi: 10.1084/jem.181.2.817. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Trinchieri G. Interleukin-12: a proinflammatory cytokine with immunoregulatory functions that bridge innate resistance and antigen-specific adaptive immunity. Annu Rev Immunol. 1995;13:251–276. doi: 10.1146/annurev.iy.13.040195.001343. [DOI] [PubMed] [Google Scholar]

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

RESOURCES