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J Biol Chem. 2012 Nov 16;287(47):39789-99. doi: 10.1074/jbc.M112.383000. Epub 2012 Sep 27.

Activation of autoreactive B cells by endogenous TLR7 and TLR3 RNA ligands.

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Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts 02118, USA.


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.

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