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RNA-associated autoantigens activate B cells by combined B cell antigen receptor/Toll-like receptor 7 engagement.

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.

Pubmed ID: 16260486


  • Lau CM
  • Broughton C
  • Tabor AS
  • Akira S
  • Flavell RA
  • Mamula MJ
  • Christensen SR
  • Shlomchik MJ
  • Viglianti GA
  • Rifkin IR
  • Marshak-Rothstein A


The Journal of experimental medicine

Publication Data

November 7, 2005

Associated Grants

  • Agency: NIAID NIH HHS, Id: AI36529
  • Agency: NIAMS NIH HHS, Id: AR050256
  • Agency: NIAMS NIH HHS, Id: AR35230

Mesh Terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Antigens, Differentiation
  • Autoantibodies
  • Autoantigens
  • B-Lymphocytes
  • Female
  • Hybridomas
  • Interferon-alpha
  • Lymphocyte Activation
  • Male
  • Membrane Glycoproteins
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred MRL lpr
  • Mice, Knockout
  • Mice, Transgenic
  • Myeloid Differentiation Factor 88
  • RNA
  • Receptors, Antigen, B-Cell
  • Receptors, Immunologic
  • Ribonucleoproteins
  • Toll-Like Receptor 7
  • Toll-Like Receptor 9