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- Title
RNA-associated autoantigens activate B cells by combined B cell antigen receptor/Toll-like receptor 7 engagement.
- Authors
Lau, Christina M; Broughton, Courtney; Tabor, Abigail S; Akira, Shizuo; Flavell, Richard A; Mamula, Mark J; Christensen, Sean R; Shlomchik, Mark J; Viglianti, Gregory A; Rifkin, Ian R; Marshak-Rothstein, Ann
- Abstract
Previous studies (Leadbetter, E.A., I.R. Rifkin, A.H. Hohlbaum, B. Beaudette, M.J. Shlomchik, and A. Marshak-Rothstein. 2002. Nature. 416:603-607; Viglianti, G.A., C.M. Lau, T.M. Hanley, B.A. Miko, M.J. Shlomchik, and A. Marshak-Rothstein. 2003. Immunity. 19:837-847) established the unique capacity of DNA and DNA-associated autoantigens to activate autoreactive B cells via sequential engagement of the B cell antigen receptor (BCR) and Toll-like receptor (TLR) 9. We demonstrate that this two-receptor paradigm can be extended to the BCR/TLR7 activation of autoreactive B cells by RNA and RNA-associated autoantigens. These data implicate TLR recognition of endogenous ligands in the response to both DNA- and RNA-associated autoantigens. Importantly, the response to RNA-associated autoantigens was markedly enhanced by IFN-alpha, a cytokine strongly linked to disease progression in patients with systemic lupus erythematosus (SLE). As further evidence that TLRs play a key role in autoantibody responses in SLE, we found that autoimmune-prone mice, lacking the TLR adaptor protein MyD88, had markedly reduced chromatin, Sm, and rheumatoid factor autoantibody titers.
- Publication
The Journal of experimental medicine, 2005, Vol 202, Issue 9, p1171
- ISSN
0022-1007
- Publication type
Journal Article
- DOI
10.1084/jem.20050630