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, Liliana Busconi, Christina M. Lau, Abigail S. Tabor, Elizabeth A. Leadbetter, Shizuo Akira, Arthur M. Krieg, Grayson B. Lipford, Gregory A. Viglianti, Ian R. Rifkin

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)247-251
Number of pages5
JournalJournal of Endotoxin Research
Volume10
Issue number4
DOIs
StatePublished - 2004
Externally publishedYes

Keywords

  • Autoreactive B cells
  • Bafilomycin A
  • Chromatin immune complexes
  • Inhibitory s-ODN
  • Toll-like receptor 9

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Molecular Biology
  • Cell Biology
  • Infectious Diseases

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    Marshak-Rothstein, A., Busconi, L., Lau, C. M., Tabor, A. S., Leadbetter, E. A., Akira, S., Krieg, A. M., Lipford, G. B., Viglianti, G. A., & Rifkin, I. R. (2004). Comparison of CpG s-ODNs, chromatin immune complexes, and dsDNA fragment immune complexes in the TLR9-dependent activation of rheumatoid factor B cells. Journal of Endotoxin Research, 10(4), 247-251. https://doi.org/10.1179/096805104225005850