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
Ann Marshak-RothsteinIan R Rifkin

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 ( approximately 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.

Citations

Aug 16, 2008·Immunologic Research·Barbara J Vilen, Jennifer A Rutan
Jul 20, 2005·The Journal of Experimental Medicine·Sean R ChristensenMark J Shlomchik
Nov 2, 2005·The Journal of Experimental Medicine·Christina M LauAnn Marshak-Rothstein
Mar 26, 2005·Immunological Reviews·Ian R RifkinAnn Marshak-Rothstein

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