DNA and RNA autoantigens as autoadjuvants
DNA and RNA autoantigens as autoadjuvants
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DOI：
10.1179/096805106x118816
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发表时间：
2006-01-01
期刊：
影响因子：
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通讯作者：
Marshak-Rothstein, Ann
中科院分区：
文献类型：
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作者：
Busconi, Liliana;Lau, Christina M.;Marshak-Rothstein, Ann
AM14 B细胞是那些低亲和力的自身反应性B细胞的原型，它们通常在外周血淋巴组织中成熟为初始细胞。这些细胞表达一种IgG2a特异性的转基因编码受体，并且可以被含有哺乳动物DNA或从死亡或垂死细胞中释放的哺乳动物RNA的免疫复合物有效激活。激活取决于b细胞受体将抗原传递到含有toll样受体-9 （TLR9）或TLR7的内部囊泡室的能力。由于TLR9和TLR7被认为优先识别微生物DNA和RNA，因此确定哺乳动物DNA和RNA在什么条件下成为有效的TLR配体，以及决定因素是递送还是结构，是很重要的。这个问题已经通过使用IgG2a单克隆抗体来递送预先加载了定义的DNA或RNA片段的免疫复合物，或通过使用修饰的odn / orn来解决。数据表明，只有某些核酸序列或结构可以诱导自身反应性b细胞增殖，即使通过b细胞受体（BCR）的摄取促进了将其递送到适当的TLR室。
AM14 B cells are a prototype for those low affinity autoreactive B cells that routinely mature as naive cells in peripheral lymphoid tissues. These cells express a transgene-encoded receptor specific for IgG2a and can be effectively activated by immune complexes that incorporate either mammalian DNA or mammalian RNA that has been released from dead or dying cells. Activation depends on the ability of the B-cell receptor to deliver antigen to an internal vesicular compartment containing either Toll-like receptor-9 (TLR9) or TLR7. Since TLR9 and TLR7 are thought to recognize microbial DNA and RNA preferentially, it is important to determine under what conditions mammalian DNA and RNA become effective TLR ligands, and whether the determining factor is delivery or structure. This issue has been addressed by using IgG2a mAbs to deliver immune complexes preloaded with defined fragments of DNA or RNA, or by using modified ODNs/ORNs. The data demonstrate that only certain nucleic acid sequences or structures can induce autoreactive B-cell proliferation, even when delivery to the appropriate TLR compartment is facilitated by uptake through the B-cell receptor (BCR).