title: Local renal autoantibody production in lupus nephritis.
abstract: Autoantibodies are central to the pathogenesis of several autoimmune diseases including systemic lupus erythematosus. Plasma cells secrete these autoantibodies, but the anatomical sites of these cells are not well defined. Here, we found that although dsDNA-specific plasma cells in NZB/W mice were present in spleen and bone marrow, a large number were in the kidneys and their number correlated with the serum dsDNA-IgG titer. We observed renal plasma cells only in mice with nephritis, where they located mainly to the tubulointerstitium of the cortex and outer medulla. These cells had the phenotypic characteristics of fully differentiated plasma cells and, similar to long-lived bone marrow plasma cells, they were not in cell cycle. In patients with lupus nephritis, plasma cells were often present in the medulla in those with the most severe disease, especially combined proliferative and membranous lupus nephritis. The identification of the kidney as a major site of autoreactive plasma cells has implications for our understanding of the pathogenesis of lupus nephritis and for strategies to deplete autoreactive plasma cells, a long-standing therapeutic aim.
authors.affiliation: Cambridge Institute for Medical Research and the Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge CB2 2OY, United Kingdom.
authors.forename: Marion
authors.initials: M
authors.lastname: Espeli
authors.forename: Susanne
authors.initials: S
authors.lastname: Bökers
authors.forename: Giovanna
authors.initials: G
authors.lastname: Giannico
authors.forename: Harriet A
authors.initials: HA
authors.lastname: Dickinson
authors.forename: Victoria
authors.initials: V
authors.lastname: Bardsley
authors.forename: Agnes B
authors.initials: AB
authors.lastname: Fogo
authors.forename: Kenneth G C
authors.initials: KG
authors.lastname: Smith
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D001323:Autoantibodies / Q000096:biosynthesis*; D001485:Basement Membrane / Q000276:immunology; D001706:Biopsy; D054377:Chemokine CXCL12 / Q000032:analysis; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D007668:Kidney / Q000276:immunology* / Q000473:pathology; D051917:Leukosialin / Q000032:analysis; D008180:Lupus Erythematosus, Systemic / Q000473:pathology; D008181:Lupus Nephritis / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008814:Mice, Inbred NZB; D010950:Plasma Cells / Q000276:immunology / Q000473:pathology
chemical_list: D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D054377:Chemokine CXCL12; D019394:Ki-67 Antigen; D051917:Leukosialin; C498355:Mki67 protein, mouse