title: B cell and/or autoantibody deficiency do not prevent neuropsychiatric disease in murine systemic lupus erythematosus.
abstract: BACKGROUND
  Neuropsychiatric lupus (NPSLE) can be one of the earliest clinical manifestations in human lupus. However, its mechanisms are not fully understood. In lupus, a compromised blood-brain barrier may allow for the passage of circulating autoantibodies into the brain, where they can induce neuropsychiatric abnormalities including depression-like behavior and cognitive abnormalities. The purpose of this study was to determine the role of B cells and/or autoantibodies in the pathogenesis of murine NPSLE.
  
  
  METHODS
  We evaluated neuropsychiatric manifestations, brain pathology, and cytokine expression in constitutively (JhD/MRL/lpr) and conditionally (hCD20-DTA/MRL/lpr, inducible by tamoxifen) B cell-depleted mice as compared to MRL/lpr lupus mice.
  
  
  RESULTS
  We found that autoantibody levels were negligible (JhD/MRL/lpr) or significantly reduced (hCD20-DTA/MRL/lpr) in the serum and cerebrospinal fluid, respectively. Nevertheless, both JhD/MRL/lpr and hCD20-DTA/MRL/lpr mice showed profound depression-like behavior, which was no different from MRL/lpr mice. Cognitive deficits were also observed in both JhD/MRL/lpr and hCD20-DTA/MRL/lpr mice, similar to those exhibited by MRL/lpr mice. Furthermore, although some differences were dependent on the timing of depletion, central features of NPSLE in the MRL/lpr strain including increased blood-brain barrier permeability, brain cell apoptosis, and upregulated cytokine expression persisted in B cell-deficient and B cell-depleted mice.
  
  
  CONCLUSIONS
  Our study surprisingly found that B cells and/or autoantibodies are not required for key features of neuropsychiatric disease in murine NPSLE.
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Wen
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Doerner
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Samantha
authors.initials: S
authors.lastname: Chalmers
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Ariel
authors.initials: A
authors.lastname: Stock
authors.affiliation: Department of Immunobiology, Yale University, New Haven, CT, USA.
authors.forename: Haowei
authors.initials: H
authors.lastname: Wang
authors.affiliation: Behavioral Core Facility, Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Gullinello
authors.affiliation: Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Shlomchik
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA. chaim.putterman@einstein.yu.edu.|Division of Rheumatology, Albert Einstein College of Medicine, F701N, 1300 Morris Park Ave, Bronx, NY, 10461, USA. chaim.putterman@einstein.yu.edu.
authors.forename: Chaim
authors.initials: C
authors.lastname: Putterman
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D001522:Behavior, Animal; D003072:Cognition Disorders / Q000209:etiology* / Q000276:immunology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D020287:In Situ Nick-End Labeling; D008180:Lupus Erythematosus, Systemic / Q000150:complications* / Q000276:immunology*; D051379:Mice; D019463:Mice, Inbred MRL lpr; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D001323:Autoantibodies
keywords: Autoantibodies; B cells; Lupus; Neuropsychiatric SLE; SLE