title: Maintenance of autoantibody production in pristane-induced murine lupus.
abstract: BACKGROUND
  Pristane-treated mice chronically produce high levels of anti-ribonucleoprotein/Smith (anti-Sm/RNP) and other lupus autoantibodies. The present study addressed how these autoantibody levels are maintained over time.
  
  
  METHODS
  Lupus was induced in BALB/c mice using pristane. Naïve B cells, switched memory B cells, switched plasmablasts, and plasma cells were flow-sorted and total IgG and anti-U1A (RNP) autoantibodies were determined with ELISA.
  
  
  RESULTS
  B cells with a switched "memory-like" (CD19(+)CD138(-)IgM(-)IgD(-)) (sMB) phenotype were increased in pristane-treated mice and expressed higher levels of Toll like receptor 7 (Tlr7) than cells with this phenotype from untreated mice. Flow-sorted sMB cells from pristane-treated mice did not secrete IgG spontaneously, but were hyper-responsive to both synthetic (R848) and natural (apoptotic cells) TLR7 ligands, resulting in increased IgG production in vitro. The flow-sorted sMB cells also could be driven by R848 to produce IgG anti-U1A autoantibodies. Production of IgG was strongly inhibited by both JSH-23 and SB203580, suggesting that the canonical NFκB and p38 MAPK pathways, respectively, contribute to the TLR7 ligand hyper-responsiveness of sMB from pristane-treated mice.
  
  
  CONCLUSIONS
  The switched memory B cell subset from pristane-treated mice is expanded and shows an increased propensity to undergo terminal (plasma cell) differentiation in response to synthetic and natural TLR7 ligands. The data suggest that the decreased clearance of apoptotic cells characteristic of pristane-treated mice might help maintain high serum levels of anti-RNP/Sm autoantibodies.
authors.affiliation: Department of Medicine, Division of Rheumatology & Clinical Immunology, University of Florida, 1600 Archer Road, Gainesville, FL, 32610-0275, USA. Shuhong.Han@medicine.ufl.edu.
authors.forename: Shuhong
authors.initials: S
authors.lastname: Han
authors.affiliation: Department of Medicine, Division of Rheumatology & Clinical Immunology, University of Florida, 1600 Archer Road, Gainesville, FL, 32610-0275, USA. Haoyang.Zhuang@medicine.ufl.edu.
authors.forename: Haoyang
authors.initials: H
authors.lastname: Zhuang
authors.affiliation: Department of Medicine, Division of Rheumatology & Clinical Immunology, University of Florida, 1600 Archer Road, Gainesville, FL, 32610-0275, USA. Yuan.Xu@medicine.ufl.edu.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Medicine, Division of Rheumatology & Clinical Immunology, University of Florida, 1600 Archer Road, Gainesville, FL, 32610-0275, USA. Pui.Lee@childrens.harvard.edu.|Current Address: Boston Children's Hospital, 300 Longwood Ave, Boston, MA, 02115, USA. Pui.Lee@childrens.harvard.edu.
authors.forename: Pui
authors.initials: P
authors.lastname: Lee
authors.affiliation: Department of Medicine, Division of Rheumatology & Clinical Immunology, University of Florida, 1600 Archer Road, Gainesville, FL, 32610-0275, USA. Yi.Li@medicine.ufl.edu.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Medicine, Division of Rheumatology & Clinical Immunology, University of Florida, 1600 Archer Road, Gainesville, FL, 32610-0275, USA. boojie_719@yahoo.com.
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Wilson
authors.affiliation: College of Pharmacy, University of Florida, Student Service Center, HPNP Complex, PO Box 100495, Gainesville, FL, 32610-0495, USA. ovidal45@ufl.edu.
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Vidal
authors.affiliation: Department of Molecular genetics and Microbiology, University of Florida, PO Box 100221, Gainesville, FL, 32610-0221, USA. hschoi@ufl.edu.
authors.forename: Hong Seok
authors.initials: HS
authors.lastname: Choi
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Florida, 1395 Center Dr., Gainesville, FL, 32610-0495, USA. sunyujn@yahoo.com.cn.|Current Address: Qilu Hospital of Shandong University, Jinan, 250012, PR China. sunyujn@yahoo.com.cn.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Florida, 1395 Center Dr., Gainesville, FL, 32610-0495, USA. yanglj@pathology.ufl.edu.
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Yang
authors.affiliation: Department of Medicine, Division of Rheumatology & Clinical Immunology, University of Florida, 1600 Archer Road, Gainesville, FL, 32610-0275, USA. Westley.reeves@medicine.ufl.edu.|Department of Pathology and Laboratory Medicine, University of Florida, 1395 Center Dr., Gainesville, FL, 32610-0495, USA. Westley.reeves@medicine.ufl.edu.
authors.forename: Westley H
authors.initials: WH
authors.lastname: Reeves
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007156:Immunologic Memory / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000139:chemically induced / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology; D013729:Terpenes / Q000276:immunology / Q000633:toxicity; D051199:Toll-Like Receptor 7 / Q000276:immunology; D055517:snRNP Core Proteins / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D008562:Membrane Glycoproteins; D013729:Terpenes; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7; D055517:snRNP Core Proteins; C009042:pristane