title: Human Plasmacytoid Dendritic Cells Display and Shed B Cell Maturation Antigen upon TLR Engagement.
abstract: The BAFF-APRIL system is best known for its control of B cell homeostasis, and it is a target of therapeutic intervention in autoimmune diseases and lymphoma. By analyzing the expression of the three receptors of this system, B cell maturation Ag (BCMA), transmembrane activator and CAML interactor, and BAFF receptor, in sorted human immune cell subsets, we found that BCMA was transcribed in plasmacytoid dendritic cells (pDCs) in both blood and lymphoid tissue. Circulating human pDCs contained BCMA protein without displaying it on the cell surface. After engagement of TLR7/8 or TLR9, BCMA was detected also on the cell surface of pDCs. The display of BCMA on the surface of human pDCs was accompanied by release of soluble BCMA (sBCMA); inhibition of γ-secretase enhanced surface expression of BCMA and reduced the release of sBCMA by pDCs. In contrast with human pDCs, murine pDCs did not express BCMA, not even after TLR9 activation. In this study, we extend the spectrum of BCMA expression to human pDCs. sBCMA derived from pDCs might determine local availability of its high-affinity ligand APRIL, because sBCMA has been shown to function as an APRIL-specific decoy. Further, therapeutic trials targeting BCMA in patients with multiple myeloma should consider possible effects on pDCs.
authors.affiliation: Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, LMU Munich, 82152 Planegg-Martinsried, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Schuh
authors.affiliation: Institute for Immunology, Biomedical Center, LMU Munich, 82152 Planegg-Martinsried, Germany.
authors.forename: Andrea
authors.identifier: 0000-0002-2497-0699
authors.initials: A
authors.lastname: Musumeci
authors.affiliation: Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, LMU Munich, 82152 Planegg-Martinsried, Germany.
authors.forename: Franziska S
authors.initials: FS
authors.lastname: Thaler
authors.affiliation: Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, LMU Munich, 82152 Planegg-Martinsried, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Laurent
authors.affiliation: Helmholtz Center, Institute of Molecular Immunology, 81675 Munich, Germany; and.
authors.forename: Joachim W
authors.initials: JW
authors.lastname: Ellwart
authors.affiliation: Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, LMU Munich, 82152 Planegg-Martinsried, Germany.|Munich Cluster for Systems Neurology (SyNergy), LMU Munich and Technical University Munich, 81377 Munich, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Hohlfeld
authors.affiliation: Institute for Immunology, Biomedical Center, LMU Munich, 82152 Planegg-Martinsried, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Krug
authors.affiliation: Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, LMU Munich, 82152 Planegg-Martinsried, Germany; edgar.meinl@med.uni-muenchen.de.
authors.forename: Edgar
authors.initials: E
authors.lastname: Meinl
mesh_terms: D000818:Animals; D053265:B-Cell Activation Factor Receptor / Q000276:immunology; D053301:B-Cell Maturation Antigen / Q000096:biosynthesis / Q000276:immunology*; D002469:Cell Separation; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D016133:Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D053265:B-Cell Activation Factor Receptor; D053301:B-Cell Maturation Antigen; C435926:TNFRSF13C protein, human