Activation of Autoreactive B Cells by Endogenous TLR7 and TLR3 RNA Ligands
Activation of Autoreactive B Cells by Endogenous TLR7 and TLR3 RNA Ligands
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DOI：
10.1074/jbc.m112.383000
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发表时间：
2012-11-16
影响因子：
4.8
通讯作者：
Marshak-Rothstein, Ann
中科院分区：
文献类型：
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作者：
Green, Nathaniel M.;Moody, Krishna-Sulayman;Marshak-Rothstein, Ann
自身反应性B细胞活化的关键步骤是含配体的核酸的内化和将这些配体递送至含Toll样受体（TLR）的内溶酶体区室。核糖核蛋白是系统性自身免疫性疾病中的一大部分自身抗原。在这里，我们证明了许多富含尿苷的哺乳动物RNA序列与共同的自身抗原有效地激活自身反应性B细胞。用I型IFN引发增加了激活的幅度，以及RNA刺激的范围。含有高度自身互补性的RNA亚组也通过TLR 3激活B细胞。对于主要通过TLR7激活的RNA序列，激活与尿苷含量成比例，并且更精确地由特定的含尿苷基序的频率定义。这些结果确定了将特定哺乳动物RNA定义为TLR配体的参数。
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.