title: A unique population of IgG-expressing plasma cells lacking CD19 is enriched in human bone marrow.
abstract: Specific serum antibodies mediating humoral immunity and autoimmunity are provided by mature plasma cells (PC) residing in the bone marrow (BM), yet their dynamics and composition are largely unclear. We here characterize distinct subsets of human PC differing by CD19 expression. Unlike CD19(+) PC, CD19(-) PC were restricted to BM, expressed predominantly IgG, and they carried a prosurvival, distinctly mature phenotype, that is, HLA-DR(low)Ki-67(-)CD95(low)CD28(+)CD56(+/-), with increased BCL2 and they resisted their mobilization from the BM after systemic vaccination. Fewer mutations within immunoglobulin VH rearrangements of CD19(-) BMPC may indicate their differentiation in early life. Their resistance to in vivo B-cell depletion, that is, their independency from supply with new plasmablasts, is consistent with long-term stability of this PC subset in the BM. Moreover, CD19(-) PC were detectable in chronically inflamed tissues and secreted autoantibodies. We propose a multilayer model of PC memory in which CD19(+) and CD19(-) PC represent dynamic and static components, respectively, permitting both adaptation and stability of humoral immune protection.
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité University Medicine Berlin, Berlin, Germany; B Cell Memory Group, German Rheumatism Research Center Berlin, a Leibniz Institute, Berlin, Germany;
authors.forename: Henrik E
authors.initials: HE
authors.lastname: Mei
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité University Medicine Berlin, Berlin, Germany; B Cell Memory Group, German Rheumatism Research Center Berlin, a Leibniz Institute, Berlin, Germany;
authors.forename: Ina
authors.initials: I
authors.lastname: Wirries
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité University Medicine Berlin, Berlin, Germany; B Cell Memory Group, German Rheumatism Research Center Berlin, a Leibniz Institute, Berlin, Germany;
authors.forename: Daniela
authors.initials: D
authors.lastname: Frölich
authors.affiliation: Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden;
authors.forename: Mikael
authors.initials: M
authors.lastname: Brisslert
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité University Medicine Berlin, Berlin, Germany; B Cell Memory Group, German Rheumatism Research Center Berlin, a Leibniz Institute, Berlin, Germany;
authors.forename: Claudia
authors.initials: C
authors.lastname: Giesecke
authors.affiliation: Bioinformatics Group, and.
authors.forename: Joachim R
authors.initials: JR
authors.lastname: Grün
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité University Medicine Berlin, Berlin, Germany; Autoimmunology Group, German Rheumatism Research Center Berlin, a Leibniz Institute, Berlin, Germany;
authors.forename: Tobias
authors.initials: T
authors.lastname: Alexander
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité University Medicine Berlin, Berlin, Germany; B Cell Memory Group, German Rheumatism Research Center Berlin, a Leibniz Institute, Berlin, Germany;
authors.forename: Stefanie
authors.initials: S
authors.lastname: Schmidt
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité University Medicine Berlin, Berlin, Germany; B Cell Memory Group, German Rheumatism Research Center Berlin, a Leibniz Institute, Berlin, Germany;
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Luda
authors.affiliation: Department of Medicine I for Gastroenterology, Infectious Diseases and Rheumatology, Charité University Medicine Berlin, Berlin, Germany;
authors.forename: Anja A
authors.initials: AA
authors.lastname: Kühl
authors.affiliation: University of Rostock, Institute of Immunology, Rostock, Germany;
authors.forename: Robby
authors.initials: R
authors.lastname: Engelmann
authors.affiliation: Department of Nephrology, Charité University Medicine Berlin, Berlin, Germany;
authors.forename: Michael
authors.initials: M
authors.lastname: Dürr
authors.affiliation: Signal Transduction Group, German Rheumatism Research Center Berlin, a Leibniz Institute, Berlin, Germany;
authors.forename: Tobias
authors.initials: T
authors.lastname: Scheel
authors.affiliation: Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden;
authors.forename: Maria
authors.initials: M
authors.lastname: Bokarewa
authors.affiliation: Department of Orthopedics, Charité University Medicine Berlin, Center for Musculoskeletal Surgery, Berlin, Germany; and.
authors.forename: Carsten
authors.initials: C
authors.lastname: Perka
authors.affiliation: Cell Biology Group, German Rheumatism Research Center Berlin, a Leibniz Institute, Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Radbruch
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité University Medicine Berlin, Berlin, Germany; B Cell Memory Group, German Rheumatism Research Center Berlin, a Leibniz Institute, Berlin, Germany;
authors.forename: Thomas
authors.initials: T
authors.lastname: Dörner
mesh_terms: D018941:Antigens, CD19 / Q000378:metabolism*; D000961:Antilymphocyte Serum / Q000008:administration & dosage; D001854:Bone Marrow Cells / Q000145:classification / Q000166:cytology* / Q000276:immunology*; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D002454:Cell Differentiation; D002470:Cell Survival; D022422:Diphtheria-Tetanus Vaccine / Q000008:administration & dosage; D006801:Humans; D056724:Immunity, Humoral; D007074:Immunoglobulin G / Q000378:metabolism*; D007156:Immunologic Memory; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D008212:Lymphocyte Depletion; D018448:Models, Immunological; D009154:Mutation; D010641:Phenotype; D010950:Plasma Cells / Q000145:classification / Q000166:cytology / Q000276:immunology*; D011719:Pyrazines / Q000008:administration & dosage; D060152:V(D)J Recombination
chemical_list: D018941:Antigens, CD19; D000961:Antilymphocyte Serum; D001897:Boronic Acids; D022422:Diphtheria-Tetanus Vaccine; D007074:Immunoglobulin G; D011719:Pyrazines; D000069286:Bortezomib