Comparison of CpG s-ODNs, chromatin immune complexes, and dsDNA fragment immune complexes in the TLR9-dependent activation of rheumatoid factor B cells.
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.
Marshak-Rothstein
Ann
A
Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, USA. amrothst@bu.edu
Busconi
Liliana
L
Lau
Christina M
CM
Tabor
Abigail S
AS
Leadbetter
Elizabeth A
EA
Akira
Shizuo
S
Krieg
Arthur M
AM
Lipford
Grayson B
GB
Viglianti
Gregory A
GA
Rifkin
Ian R
IR
D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology*; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology*; D018899:CpG Islands / Q000235:genetics*; D004247:DNA; D004268:DNA-Binding Proteins / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D018942:Macrolides / Q000494:pharmacology; D051379:Mice; D009838:Oligodeoxyribonucleotides; D011956:Receptors, Cell Surface; D012217:Rheumatoid Factor / Q000502:physiology*; D051217:Toll-Like Receptor 9
D000936:Antigen-Antibody Complex; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D018942:Macrolides; D009838:Oligodeoxyribonucleotides; D011956:Receptors, Cell Surface; C495371:TLR9 protein, human; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; C057620:bafilomycin A; D004247:DNA; D012217:Rheumatoid Factor