Bone Marrow Stromal Cell Antigen 2 Is a Specific Marker of Type I IFN-Producing Cells in the Naive Mouse, but a Promiscuous Cell Surface Antigen following IFN Stimulation1

Type I IFN-producing cells (IPC) are sentinels of viral infections. Identification and functional characterization of these cells have been difficult because of their small numbers in blood and tissues and their complex cell surface phenotype. To overcome this problem in mice, mAbs recognizing IPC-specific cell surface molecules have been generated. In this study, we report the identification of new Abs specific for mouse IPC, which recognize the bone marrow stromal cell Ag 2 (BST2). Interestingly, previously reported IPC-specific Abs 120G8 and plasmacytoid dendritic cell Ag-1 also recognize BST2. BST2 is predominantly specific for mouse IPC in naive mice, but is up-regulated on most cell types following stimulation with type I IFNs and IFN-γ. The activation-induced promiscuous expression of BST2 described in this study has important implications for the use of anti-BST2 Abs in identification and depletion of IPC. Finally, we show that BST2 resides within an intracellular compartment corresponding to the Golgi apparatus, and may be involved in trafficking secreted cytokines in IPC.

[1]  Vincenzo Cerundolo,et al.  Characterization of Siglec-H as a novel endocytic receptor expressed on murine plasmacytoid dendritic cell precursors. , 2006, Blood.

[2]  M. Colonna,et al.  Siglec-H is an IPC-specific receptor that modulates type I IFN secretion through DAP12. , 2006, Blood.

[3]  S. Akira,et al.  Pathogen Recognition and Innate Immunity , 2006, Cell.

[4]  Yubin Ge,et al.  Differential gene expression, GATA1 target genes, and the chemotherapy sensitivity of Down syndrome megakaryocytic leukemia. , 2006, Blood.

[5]  T. Mak,et al.  Adhesive mechanisms governing interferon-producing cell recruitment into lymph nodes , 2005, The Journal of experimental medicine.

[6]  J. Petriz,et al.  Characterization of antibodies submitted to the B cell section of the 8th Human Leukocyte Differentiation Antigens Workshop by flow cytometry and immunohistochemistry. , 2005, Cellular immunology.

[7]  Y. Omatsu,et al.  Development of Murine Plasmacytoid Dendritic Cells Defined by Increased Expression of an Inhibitory NK Receptor, Ly49Q1 , 2005, The Journal of Immunology.

[8]  H. Sorimachi,et al.  Inhibitory NK Receptor Ly49Q Is Expressed on Subsets of Dendritic Cells in a Cellular Maturation- and Cytokine Stimulation-Dependent Manner1 , 2005, The Journal of Immunology.

[9]  G. Trinchieri,et al.  Type I interferon dependence of plasmacytoid dendritic cell activation and migration , 2005, The Journal of experimental medicine.

[10]  K. Arai,et al.  Ly49Q defines 2 pDC subsets in mice. , 2005, Blood.

[11]  W. Ouyang,et al.  Proteomic profiling of surface proteins on Th1 and Th2 cells. , 2005, Journal of proteome research.

[12]  Yong‐jun Liu,et al.  IPC: professional type 1 interferon-producing cells and plasmacytoid dendritic cell precursors. , 2005, Annual review of immunology.

[13]  G. Trinchieri,et al.  Plasmacytoid dendritic cells in immunity , 2004, Nature Immunology.

[14]  Asma Nusrat,et al.  Association of BAP31 with CD11b/CD18 , 2004, Journal of Biological Chemistry.

[15]  A. Iwasaki,et al.  Toll-like receptor control of the adaptive immune responses , 2004, Nature Immunology.

[16]  M. Colonna,et al.  A cell-surface molecule selectively expressed on murine natural interferon-producing cells that blocks secretion of interferon-alpha. , 2004, Blood.

[17]  G. Trinchieri,et al.  Mouse Strain Differences in Plasmacytoid Dendritic Cell Frequency and Function Revealed by a Novel Monoclonal Antibody , 2003, Journal of Immunology.

[18]  George Banting,et al.  Bst‐2/HM1.24 Is a Raft‐Associated Apical Membrane Protein with an Unusual Topology , 2003, Traffic.

[19]  R. Teasdale,et al.  Intracellular sorting and transport of proteins. , 2003, Progress in biophysics and molecular biology.

[20]  S. Sugano,et al.  Large-scale identification and characterization of human genes that activate NF-κB and MAPK signaling pathways , 2003, Oncogene.

[21]  C. Arias,et al.  Characterization of a new subpopulation of mouse CD8alpha+ B220+ dendritic cells endowed with type 1 interferon production capacity and tolerogenic potential. , 2002, Blood.

[22]  Antonio Lanzavecchia,et al.  BDCA-2, a Novel Plasmacytoid Dendritic Cell–specific Type II C-type Lectin, Mediates Antigen Capture and Is a Potent Inhibitor of Interferon α/β Induction , 2001, The Journal of experimental medicine.

[23]  P Björck,et al.  Isolation and characterization of plasmacytoid dendritic cells from Flt3 ligand and granulocyte-macrophage colony-stimulating factor-treated mice. , 2001, Blood.

[24]  Marc Dalod,et al.  Mouse type I IFN-producing cells are immature APCs with plasmacytoid morphology , 2001, Nature Immunology.

[25]  M. Gunn,et al.  Cd11c+B220+Gr-1+ Cells in Mouse Lymph Nodes and Spleen Display Characteristics of Plasmacytoid Dendritic Cells , 2001, The Journal of experimental medicine.

[26]  M. Tsuchiya,et al.  Molecular cloning and characterization of a surface antigen preferentially overexpressed on multiple myeloma cells. , 1999, Biochemical and biophysical research communications.

[27]  A. Lanzavecchia,et al.  Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacity: T-T help via APC activation , 1996, The Journal of experimental medicine.

[28]  M. Reth,et al.  The specificity of association of the IgD molecule with the accessory proteins BAP31/BAP29 lies in the IgD transmembrane sequence. , 1996, The EMBO journal.

[29]  J. Inazawa,et al.  Molecular cloning and chromosomal mapping of a bone marrow stromal cell surface gene, BST2, that may be involved in pre-B-cell growth. , 1995, Genomics.

[30]  S. Kennel,et al.  A novel membrane antigen selectively expressed on terminally differentiated human B cells. , 1994, Blood.

[31]  M. Reth,et al.  Two new proteins preferentially associated with membrane immunoglobulin D. , 1994, The EMBO journal.

[32]  M Aguet,et al.  Functional role of type I and type II interferons in antiviral defense. , 1994, Science.