RNA-associated autoantigens activate B cells by combined B cell antigen receptor/Toll-like receptor 7 engagement
Copyright policy )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-α, 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.
- Boston College United States
- Yale University United States
- Department of Microbiology United States
- Osaka University Japan
- Boston University United States
Male, Mice, Knockout, B-Lymphocytes, Mice, Inbred MRL lpr, Hybridomas, Membrane Glycoproteins, Brief Definitive Report, Interferon-alpha, Receptors, Antigen, B-Cell, Mice, Transgenic, Lymphocyte Activation, Antigens, Differentiation, Autoantigens, Mice, Inbred C57BL, Mice, Myeloid Differentiation Factor 88, Animals, RNA, Female, Adaptor Proteins, Signal Transducing, Autoantibodies
Male, Mice, Knockout, B-Lymphocytes, Mice, Inbred MRL lpr, Hybridomas, Membrane Glycoproteins, Brief Definitive Report, Interferon-alpha, Receptors, Antigen, B-Cell, Mice, Transgenic, Lymphocyte Activation, Antigens, Differentiation, Autoantigens, Mice, Inbred C57BL, Mice, Myeloid Differentiation Factor 88, Animals, RNA, Female, Adaptor Proteins, Signal Transducing, Autoantibodies
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