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- Title
B cell and/or autoantibody deficiency do not prevent neuropsychiatric disease in murine systemic lupus erythematosus.
- Authors
Jing Wen; Doerner, Jessica; Chalmers, Samantha; Stock, Ariel; Haowei Wang; Gullinello, Maria; Shlomchik, Mark J.; Putterman, Chaim; Wen, Jing; Wang, Haowei
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>Our study surprisingly found that B cells and/or autoantibodies are not required for key features of neuropsychiatric disease in murine NPSLE.
- Subjects
SYSTEMIC lupus erythematosus; B cells; AUTOANTIBODIES; CYTOKINES; COGNITION disorders research; APOPTOSIS; ANIMAL behavior; ANIMAL experimentation; BIOLOGICAL models; COGNITION disorders; COMPARATIVE studies; ENZYME-linked immunosorbent assay; FLOW cytometry; FLUORESCENT antibody technique; GENETIC techniques; RESEARCH methodology; MEDICAL cooperation; MICE; POLYMERASE chain reaction; RESEARCH; RESEARCH funding; EVALUATION research; DISEASE complications
- Publication
Journal of Neuroinflammation, 2016, Vol 13, p1
- ISSN
1742-2094
- Publication type
journal article
- DOI
10.1186/s12974-016-0537-3