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Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 1/2015

Open Access 01-12-2015 | Research article

Maintenance of autoantibody production in pristane-induced murine lupus

Authors: Shuhong Han, Haoyang Zhuang, Yuan Xu, Pui Lee, Yi Li, Joseph C. Wilson, Osvaldo Vidal, Hong Seok Choi, Yu Sun, Li-Jun Yang, Westley H. Reeves

Published in: Arthritis Research & Therapy | Issue 1/2015

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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.
Appendix
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Metadata
Title
Maintenance of autoantibody production in pristane-induced murine lupus
Authors
Shuhong Han
Haoyang Zhuang
Yuan Xu
Pui Lee
Yi Li
Joseph C. Wilson
Osvaldo Vidal
Hong Seok Choi
Yu Sun
Li-Jun Yang
Westley H. Reeves
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 1/2015
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/s13075-015-0886-9

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