B Lymphocytes as Antigen-Presenting Cells for CD4+ T Cell Priming In Vivo

Journal of Immunology - Tập 162 Số 10 - Trang 5695-5703 - 1999
Stephanie L. Constant1
1Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520

Tóm tắt

Abstract The contribution of B lymphocytes as APCs for CD4+ T cell priming remains controversial, based on findings that B cells cannot provide the requisite ligating and costimulatory signals for naive T cells to be activated. In the current study, we have examined Ag-specific T:B cell collaboration under circumstances in which B cells take up Ag through Ig receptors in vivo. This results in their activation and an ability to effectively stimulate naive CD4+ T cells both in vitro and in vivo. The aim of this work was to establish some of the key molecular interactions, as well as kinetics, between Ag-specific T and B cells that enable this priming to take place. Our approach was to amplify the starting pools of both Ag-specific T and B cell populations in vivo to track directly the events during initial T:B cell collaborations. We show that the induction of optimal levels of T cell priming to a protein Ag requires the involvement of Ag-specific B cells. The interaction that results between Ag-specific T and B cells prevents the down-modulation of B7 costimulatory molecules usually observed in the absence of appropriate T cells. Moreover, this prevention in down-modulation is independent of CD40:CD40 ligand contact. Finally, we present data suggesting that once Ag-specific T and B cells interact, there is a rapid (1–2-h) down-regulation of antigenic complexes on the surface of the B lymphocytes, possibly to prevent them from engaging other T cells in the vicinity and therefore focus the initial interaction.

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Tài liệu tham khảo

Healy, J. I., C. C. Goodnow. 1998. Positive versus negative signaling by lymphocyte antigen receptors. Annu. Rev. Immunol. 16: 645

Ashwell, J. D.. 1988. Are B lymphocytes the principal antigen-presenting cells in vivo?. J. Immunol. 140: 3697

Levin, D., S. Constant, T. Pasqualini, R. Flavell, K. Bottomly. 1993. Role of dendritic cells in the priming of CD4+ T lymphocytes to peptide antigen in vivo. J. Immunol. 151: 6742

Wilson, J. L., A. C. Cunningham, J. A. Kirby. 1995. Alloantigen presentation by B cells: analysis of the requirement for B-cell activation. Immunology 86: 325

Lassila, O., S. Vainio, P. Matzinger. 1988. Can B cells turn on virgin T cells?. Nature 334: 253

Eynon, E. E., D. C. Parker. 1992. Small B cells as antigen-presenting cells in the induction of tolerance to soluble protein antigens. J. Exp. Med. 175: 131

Noelle, R. J., E. C. Snow, J. W. Uhr, E. S. Vitetta. 1983. Activation of antigen-specific B cells: role of T cells, cytokines, and antigen in induction of growth and differentiation. Proc. Natl. Acad. Sci. USA 80: 6628

Grewal, I. S., R. A. Flavell. 1998. CD40 and CD154 in cell-mediated immunity. Annu. Rev. Immunol. 16: 111

Inaba, K., R. M. Steinman. 1984. Resting and sensitized T lymphocytes exhibit distinct stimulatory (antigen-presenting cell) requirements for growth and lymphokine release. J. Exp. Med. 160: 1717

Croft, M., S. L. Swain. 1991. B cell response to fresh and effector helper T cells: a role of cognate T-B interaction and the cytokines IL-2, IL-4, and IL-6. J. Immunol. 146: 4055

Fuchs, F. J., P. Matzinger. 1992. B cells turn off virgin but not memory T cells. Science 258: 1156

Dubey, C., M. Croft, S. L. Swain. 1995. Costimulatory requirements of naive CD4+ T cells: ICAM-1 or B7-1 can costimulate naive CD4+ T cell activation but both are required for optimum response. J. Immunol. 155: 45

Eynon, E. E., D. C. Parker. 1993. Parameters of tolerance induction by antigen targeted to B lymphocytes. J. Immunol. 151: 2958

Morris, S. C., A. Lees, F. D. Finkelman. 1994. In vivo activation of naive T cells by anitgen-presenting B cells. J. Immunol. 152: 3777

Constant, C., N. Schweitzer, J. West, P. Ranney, K. Bottomly. 1995. B lymphocytes can be competent antigen presenting cells for priming CD4+ T cells to protein antigens in vivo. J. Immunol. 155: 3734

Goodnow, C. C., J. Crosbie, S. Adelstein, T. B. Lavoie, S. J. Smith-Gill, R. Brink, H. Pritchard-Briscoe, J. Wotherspoon, R. Loblay, K. Raphael, R. Trent, A. Basten. 1988. Altered immunoglobulin expression and functional silencing of self-reactive B lymphocytes in transgenic mice. Nature 334: 676

Kaye, J., M.-L. Hsa, M.-E. Sauron, S. C. Jameson, N. Gascoigne, S. M. Hedrik. 1989. Selective development of CD4+ T cells in transgenic mice express a class II MHC restricted antigen receptor. Nature 341: 746

Xu, J., T. M. Foy, J. D. Laman, E. A. Elliott, J. J. Dunn, T. J. Waldschmidt, J. Elsemore, R. J. Noelle, R. A. Flavell. 1994. Mice deficient for the CD40 ligand. Immunity 1: 423

Lyons, A. B., C. R. Parish. 1994. Determination of lymphocyte division by flow cytometry. J. Immunol. Methods 171: 131

Constant, S., D. Sant’Angelo, T. Pasqualini, T. Taylor, D. Levin, R. Flavell, K. Bottomly. 1995. Peptide and protein antigens require distinct antigen presenting cell subsets for the priming of CD4+ T cells. J. Immunol. 154: 4915

Garside, P., E. Ingulli, R. R. Merica, J. G. Johnson, R. J. Noelle, M. K. Jenkins. 1998. Visualization of specific B and T lymphocyte interactions in the lymph node. Science 281: 96

Stossel, H., F. Koch, E. Kampgen, P. Stoger, A. Lenz, C. Heufler, N. Romani, G. Schuler. 1990. Disappearance of certain acidic organelles (endosomes and Langerhans cell granules) accompanies loss of antigen processing capacity upon culture of epidermal Langerhans cells. J. Exp. Med. 172: 1471

Knight, S. C., A. J. Stagg. 1993. Antigen-presenting cell types. Curr. Opin. Immunol. 5: 374

Jiang, W., W. J. Swiggard, C. Heufler, M. Peng, A. Mirza, R. M. Steinman, M. C. Nussenzweig. 1995. The receptor DEC-205 expressed by dendritic cells and thymic epithelial cells is involved in antigen processing. Nature 375: 151

Banchereau, J., F. Bazan, D. Blanchard, F. Briere, J. P. Galizzi, C. van Kooten, Y. J. Liu, F. Rousset, S. Saeland. 1994. The CD40 antigen and its ligand. Annu. Rev. Immunol. 12: 881

Grabstein, K. H., C. R. Maliszewski, K. Shanebeck, T. A. Sato, M. K. Spriggs, W. C. Fanslow, R. J. Armitage. 1993. The regulation of T cell-dependent antibody formation in vitro by CD40 ligand and IL-2. J. Immunol. 150: 3141

Roy, M., A. Aruffo, J. Ledbetter, P. Linsley, M. Kehry, R. Noelle. 1995. Studies on the interdependence of gp39 and B7 expression and function during antigen-specific immune responses. Eur. J. Immunol. 25: 596

Lenschow, D. J., A. I. Sperling, M. P. Cooke, G. Freeman, L. Rhee, D. C. Decker, G. Gray, L. M. Nadler, C. C. Goodnow, J. A. Bluestone. 1994. Differential up-regulation of the B7-1 and B7-2 costimulatory molecules after Ig receptor engagement by antigen. J. Immunol. 153: 1990

Grewal, I. S., J. Xu, R. A. Flavell. 1995. Impairment of antigen-specific T-cell priming in mice lacking CD40 ligand. Nature 378: 617

Song, W., H. Cho, P. Cheng, S. K. Pierce. 1995. Entry of B cell antigen receptor and antigen into class II peptide-loading compartment is independent of receptor cross-linking. J. Immunol. 155: 4255

Cyster, J. G., C. C. Goodnow. 1995. Antigen-induced exclusion from follicles and anergy are separate and complementary processes that influence peripheral B cell fate. Immunity 3: 691

Fulcher, D. A., A. B. Lyons, S. L. Korn, M. C. Cook, C. Koleda, C. Parish, B. Fazekas de St. Groth, A. Basten. 1996. The fate of self-reactive B cells depends primarily on the degree of antigen receptor engagement and availability of T cell help. J. Exp. Med. 183: 2313

Fournier, S., J. C. Rathmell, C. G. Goodnow, J. P. Allison. 1997. T cell-mediated elimination of B7.2 transgenic B cells. Immunity 6: 327

Townsend, S. E., C. C. Goodnow. 1998. Abortive proliferation of rare T cells induced by direct or indirect antigen presentation by rare B cells in vivo. J. Exp. Med. 187: 1611

Klinman, N. R., J. L. Press. 1975. The B cell specificity repertoire: its relationship to definable subpopulations. Transplant. Rev. 24: 41

Liu, Y. J., J. Zhang, P. J. L. Lane, E. Y. T. Chan, I. C. M. MacLennan. 1991. Sites of specific B cell activation in primary and secondary responses to T cell-dependent and T cell-independent antigens. Eur. J. Immunol. 21: 2951

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Journal of Immunology

Tập 162 Số 10

5695-5703

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