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Journal of Endotoxin Research
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Comparison of CpG s-ODNs, chromatin immune complexes, and dsDNA fragment immune complexes in the TLR9-dependent activation of rheumatoid factor B cells

Ann Marshak-Rothstein

Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, USA, amrothst{at}bu.edu

Liliana Busconi

Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, USA

Christina M. Lau

Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, USA

Abigail S. Tabor

Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, USA

Elizabeth A. Leadbetter

Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA

Shizuo Akira

Research Institute for Microbial Diseases, Osaka University, Osaka, Japan

Arthur M. Krieg

Coley Pharmaceutical Group, Wellesley, Massachusetts, USA

Grayson B. Lipford

Coley Pharmaceutical Group, Wellesley, Massachusetts, USA

Gregory A. Viglianti

Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, USA

Ian R. Rifkin

Renal Section, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA

Synthetic single-stranded oligodeoxynucleotides (15—30 bp) containing CpG motifs and phosphorothioate backbones (CpG s-ODN), immune complexes consisting of anti-nucleosome mAbs and mammalian chromatin (chromatin IC), and immune complexes consisting of anti-hapten mAbs and haptenated-double stranded DNA fragments (~600 bp) can all effectively stimulate transgenic B cells expressing a rheumatoid factor receptor by a TLR9-dependent process. However, differential sensitivity to both s-ODN and small molecule inhibitors suggests that stimulatory CpG sODN and chromatin IC may either access TLR9 via different routes or depend on discrete activation parameters. These data have important implications regarding the therapeutic application of TLR9 inhibitors to the treatment of systemic autoimmune diseases.

Key Words: Autoreactive B cells • bafilomycin A • chromatin immune complexes • inhibitory s-ODN • Toll-like receptor 9

Journal of Endotoxin Research, Vol. 10, No. 4, 247-251 (2004)
DOI: 10.1177/09680519040100040801
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