title: Activation of autoreactive B cells by endogenous TLR7 and TLR3 RNA ligands.
abstract: The key step in the activation of autoreactive B cells is the internalization of nucleic acid containing ligands and delivery of these ligands to the Toll-like Receptor (TLR) containing endolysosomal compartment. Ribonucleoproteins represent a large fraction of autoantigens in systemic autoimmune diseases. Here we demonstrate that many uridine-rich mammalian RNA sequences associated with common autoantigens effectively activate autoreactive B cells. Priming with type I IFN increased the magnitude of activation, and the range of which RNAs were stimulatory. A subset of RNAs that contain a high degree of self-complementarity also activated B cells through TLR3. For the RNA sequences that activated predominantly through TLR7, the activation is proportional to uridine-content, and more precisely defined by the frequency of specific uridine-containing motifs. These results identify parameters that define specific mammalian RNAs as ligands for TLRs.
authors.affiliation: Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
authors.forename: Nathaniel M
authors.initials: NM
authors.lastname: Green
authors.forename: Krishna-Sulayman
authors.initials: KS
authors.lastname: Moody
authors.forename: Michelle
authors.initials: M
authors.lastname: Debatis
authors.forename: Ann
authors.initials: A
authors.lastname: Marshak-Rothstein
mesh_terms: D000818:Animals; D015551:Autoimmunity; D008024:Ligands; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D012313:RNA / Q000235:genetics / Q000276:immunology*; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000276:immunology*; D051199:Toll-Like Receptor 7 / Q000235:genetics / Q000276:immunology*; D014529:Uridine / Q000235:genetics / Q000276:immunology
chemical_list: D008024:Ligands; D008562:Membrane Glycoproteins; C519703:TLR3 protein, mouse; C477038:Tlr7 protein, mouse; D051196:Toll-Like Receptor 3; D051199:Toll-Like Receptor 7; D012313:RNA; D014529:Uridine