title: High frequency of autoantibody-secreting cells and long-lived plasma cells within inflamed kidneys of NZB/W F1 lupus mice.
abstract: Autoantibodies to double-stranded (ds) DNA represent a serological hallmark of systemic lupus erythematosus (SLE) and may critically contribute to the pathogenesis of lupus nephritis. Self-reactive antibodies might be partially produced by long-lived plasma cells (PCs), which mainly reside within the bone marrow and spleen. In contrast to short-lived PCs, long-lived PCs are extremely resistant to therapy and may sustain refractory disease courses. Recently, antibody-secreting cells were found within the inflamed kidneys of New Zealand black/white (NZB/W) F1 lupus mice as well as of patients with SLE. To analyze the longevity of the IgG-producing cells present in nephritic kidneys of NZB/W F1 mice we performed in vivo BrdU-labeling. We identified a higher frequency of long-lived than short-lived renal PCs, indicating that survival niches for long-lived PCs also exist within inflamed kidneys. Using ELISPOT assays, we found that on average 31% of renal IgG-producing cells reacted with dsDNA and 24% with nucleolin. Moreover, the frequencies of IgG-secreting cells specific for the autoantigens dsDNA and nucleolin were higher in the kidneys compared with those in the spleen and bone marrow.
authors.affiliation: Department of Internal Medicine 3, Clinical Research Group, Nikolaus-Fiebiger Center of Molecular Medicine, University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Starke
authors.forename: Silke
authors.initials: S
authors.lastname: Frey
authors.forename: Ute
authors.initials: U
authors.lastname: Wellmann
authors.forename: Vilma
authors.initials: V
authors.lastname: Urbonaviciute
authors.forename: Martin
authors.initials: M
authors.lastname: Herrmann
authors.forename: Kerstin
authors.initials: K
authors.lastname: Amann
authors.forename: Georg
authors.initials: G
authors.lastname: Schett
authors.forename: Thomas
authors.initials: T
authors.lastname: Winkler
authors.forename: Reinhard E
authors.initials: RE
authors.lastname: Voll
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis* / Q000276:immunology; D000921:Antibody-Producing Cells / Q000276:immunology*; D001323:Autoantibodies / Q000096:biosynthesis* / Q000276:immunology; D001853:Bone Marrow / Q000276:immunology; D001973:Bromodeoxyuridine / Q000378:metabolism; D002470:Cell Survival; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D005434:Flow Cytometry; D007074:Immunoglobulin G / Q000096:biosynthesis; D007668:Kidney / Q000276:immunology* / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000473:pathology; D008181:Lupus Nephritis / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008814:Mice, Inbred NZB; D010750:Phosphoproteins / Q000276:immunology; D010950:Plasma Cells / Q000276:immunology*; D016601:RNA-Binding Proteins / Q000276:immunology; D013154:Spleen / Q000276:immunology; D000097796:Nucleolin
chemical_list: D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D001973:Bromodeoxyuridine; D007074:Immunoglobulin G; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D000097796:Nucleolin