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Original Article

BDCA-2, a Novel Plasmacytoid Dendritic Cell–specific Type II C-type Lectin, Mediates Antigen Capture and Is a Potent Inhibitor of Interferon /ß Induction

¹ Miltenyi Biotec GmbH, D-51429 Bergisch Gladbach, Germany
² Pharmaceutical Research Laboratory, Kirin Brewery Company, Limited, Gunma 370-1295, Japan
³ Basel Institute for Immunology, CH-4005 Basel, Switzerland
⁴ Department of Pathology, University of Brescia, Spedali Civili Brescia, 1-25124 Brescia, Italy
⁵ Institute for Research in Biomedicine, CH-6500 Bellinzona, Switzerland

Address correspondence to J. Schmitz, Miltenyi Biotec GmbH, Friedrich-Ebert-Strabe 68, D-51429 Bergisch Gladbach, Germany. Phone: 49-2204-8306-410; Fax: 49-2204-85197; E-mail: juergenS{at}miltenyibiotec.de

Plasmacytoid dendritic cells are present in lymphoid and nonlymphoid tissue and contribute substantially to both innate and adaptive immunity. Recently, we have described several monoclonal antibodies that recognize a plasmacytoid dendritic cell-specific antigen, which we have termed BDCA-2. Molecular cloning of BDCA-2 revealed that BDCA-2 is a novel type II C-type lectin, which shows 50.7% sequence identity at the amino acid level to its putative murine ortholog, the murine dendritic cell–associated C-type lectin 2. Anti–BDCA-2 monoclonal antibodies are rapidly internalized and efficiently presented to T cells, indicating that BDCA-2 could play a role in ligand internalization and presentation. Furthermore, ligation of BDCA-2 potently suppresses induction of interferon /ß production in plasmacytoid dendritic cells, presumably by a mechanism dependent on calcium mobilization and protein-tyrosine phosphorylation by src-family protein-tyrosine kinases. Inasmuch as production of interferon /ß by plasmacytoid dendritic cells is considered to be a major pathophysiological factor in systemic lupus erythematosus, triggering of BDCA-2 should be evaluated as therapeutic strategy for blocking production of interferon /ß in systemic lupus erythematosus patients.

Key Words: interferon type I • monoclonal antibodies • magnetic cell sorting • interferon inducers • systemic lupus erythematosus

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• Kim, S., McAuliffe, W. J., Zaritskaya, L. S., Moore, P. A., Zhang, L., Nardelli, B. (2004). Selective Induction of Tumor Necrosis Receptor Factor 6/Decoy Receptor 3 Release by Bacterial Antigens in Human Monocytes and Myeloid Dendritic Cells. Infect. Immun. 72: 89-93 [Abstract] [Full Text]  
• Asselin-Paturel, C., Brizard, G., Pin, J.-J., Briere, F., Trinchieri, G. (2003). Mouse Strain Differences in Plasmacytoid Dendritic Cell Frequency and Function Revealed by a Novel Monoclonal Antibody. J. Immunol. 171: 6466-6477 [Abstract] [Full Text]  
• Klimstra, W. B., Nangle, E. M., Smith, M. S., Yurochko, A. D., Ryman, K. D. (2003). DC-SIGN and L-SIGN Can Act as Attachment Receptors for Alphaviruses and Distinguish between Mosquito Cell- and Mammalian Cell-Derived Viruses. J. Virol. 77: 12022-12032 [Abstract] [Full Text]  
• Turville, S., Wilkinson, J., Cameron, P., Dable, J., Cunningham, A. L. (2003). The role of dendritic cell C-type lectin receptors in HIV pathogenesis. J. Leukoc. Biol. 74: 710-718 [Abstract] [Full Text]  
• Teleshova, N., Frank, I., Pope, M. (2003). Immunodeficiency virus exploitation of dendritic cells in the early steps of infection. J. Leukoc. Biol. 74: 683-690 [Abstract] [Full Text]  
• Hartmann, E., Wollenberg, B., Rothenfusser, S., Wagner, M., Wellisch, D., Mack, B., Giese, T., Gires, O., Endres, S., Hartmann, G. (2003). Identification and Functional Analysis of Tumor-Infiltrating Plasmacytoid Dendritic Cells in Head and Neck Cancer. Cancer Res. 63: 6478-6487 [Abstract] [Full Text]  
• Bave, U., Magnusson, M., Eloranta, M.-L., Perers, A., Alm, G. V., Ronnblom, L. (2003). Fc{gamma}RIIa Is Expressed on Natural IFN-{alpha}-Producing Cells (Plasmacytoid Dendritic Cells) and Is Required for the IFN-{alpha} Production Induced by Apoptotic Cells Combined with Lupus IgG. J. Immunol. 171: 3296-3302 [Abstract] [Full Text]  
• kanazawa, N., Tashiro, K., Inaba, K., Miyachi, Y. (2003). Dendritic Cell Immunoactivating Receptor, a Novel C-type Lectin Immunoreceptor, Acts as an Activating Receptor through Association with Fc Receptor {gamma} Chain. J. Biol. Chem. 278: 32645-32652 [Abstract] [Full Text]  
• Kerkmann, M., Rothenfusser, S., Hornung, V., Towarowski, A., Wagner, M., Sarris, A., Giese, T., Endres, S., Hartmann, G. (2003). Activation with CpG-A and CpG-B Oligonucleotides Reveals Two Distinct Regulatory Pathways of Type I IFN Synthesis in Human Plasmacytoid Dendritic Cells. J. Immunol. 170: 4465-4474 [Abstract] [Full Text]  
• Miller, J. L., Anders, E. M. (2003). Virus-cell interactions in the induction of type 1 interferon by influenza virus in mouse spleen cells. J. Gen. Virol. 84: 193-202 [Abstract] [Full Text]  
• Bonifaz, L., Bonnyay, D., Mahnke, K., Rivera, M., Nussenzweig, M. C., Steinman, R. M. (2002). Efficient Targeting of Protein Antigen to the Dendritic Cell Receptor DEC-205 in the Steady State Leads to Antigen Presentation on Major Histocompatibility Complex Class I Products and Peripheral CD8+ T Cell Tolerance. JEM 196: 1627-1638 [Abstract] [Full Text]  
• Schiffer, L E, Hussain, N, Wang, X, Huang, W, Sinha, J, Ramanujam, M, Davidson, A (2002). Lowering anti-dsDNA antibodies--what's new?. Lupus 11: 885-894 [Abstract]  
• Schjetne, K. W., Thompson, K. M., Aarvak, T., Fleckenstein, B., Sollid, L. M., Bogen, B. (2002). A mouse C{kappa}-specific T cell clone indicates that DC-SIGN is an efficient target for antibody-mediated delivery of T cell epitopes for MHC class II presentation. Int Immunol 14: 1423-1430 [Abstract] [Full Text]  
• Ryan, E. J., Marshall, A. J., Magaletti, D., Floyd, H., Draves, K. E., Olson, N. E., Clark, E. A. (2002). Dendritic Cell-Associated Lectin-1: A Novel Dendritic Cell-Associated, C-Type Lectin-Like Molecule Enhances T Cell Secretion of IL-4. J. Immunol. 169: 5638-5648 [Abstract] [Full Text]  
• Nardelli, B., Zaritskaya, L., Semenuk, M., Cho, Y. H., LaFleur, D. W., Shah, D., Ullrich, S., Girolomoni, G., Albanesi, C., Moore, P. A. (2002). Regulatory Effect of IFN-{kappa}, A Novel Type I IFN, On Cytokine Production by Cells of the Innate Immune System. J. Immunol. 169: 4822-4830 [Abstract] [Full Text]  
• Ebner, S., Hofer, S., Nguyen, V. A., Furhapter, C., Herold, M., Fritsch, P., Heufler, C., Romani, N. (2002). A Novel Role for IL-3: Human Monocytes Cultured in the Presence of IL-3 and IL-4 Differentiate into Dendritic Cells That Produce Less IL-12 and Shift Th Cell Responses Toward a Th2 Cytokine Pattern. J. Immunol. 168: 6199-6207 [Abstract] [Full Text]  
• Geijtenbeek, T. B. H., Engering, A., van Kooyk, Y. (2002). DC-SIGN, a C-type lectin on dendritic cells that unveils many aspects of dendritic cell biology. J. Leukoc. Biol. 71: 921-931 [Abstract] [Full Text]  
• Iyoda, T., Shimoyama, S., Liu, K., Omatsu, Y., Akiyama, Y., Maeda, Y., Takahara, K., Steinman, R. M., Inaba, K. (2002). The CD8+ Dendritic Cell Subset Selectively Endocytoses Dying Cells in Culture and In Vivo. JEM 195: 1289-1302 [Abstract] [Full Text]  

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