CPG MOTIFS IN BACTERIAL-DNA TRIGGER DIRECT B-CELL ACTIVATION
CPG MOTIFS IN BACTERIAL-DNA TRIGGER DIRECT B-CELL ACTIVATION
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DOI：
10.1038/374546a0
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发表时间：
1995-04-06
期刊：
影响因子：
64.8
通讯作者：
KLINMAN, DM
中科院分区：
文献类型：
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作者：
KRIEG, AM;YI, AK;KLINMAN, DM
未甲基化的CpG二核苷酸在细菌和病毒基因组中比在脊椎动物基因组中更常见。我们在这里报道了细菌DNA和含有未甲基化CPG二核苷酸的合成寡脱氧核苷酸诱导小鼠B细胞增殖和分泌免疫球蛋白的实验。通过抗原受体传递的同步信号增强了这种激活。最佳的b细胞激活需要一个DNA基序，其中一个未甲基化的CpG二核苷酸的两侧是两个5‘嘌呤和两个3’嘧啶。含有该CpG基序的寡脱氧核苷酸诱导95%以上的脾脏B细胞进入细胞周期。这些数据表明，在脊椎动物中，基于微生物DNA识别的免疫防御与CpG抑制现象之间可能存在进化联系。CpG寡核苷酸的有效免疫激活对使用“反义”寡核苷酸的研究的设计和解释具有重要意义，并指出了作为佐剂的可能的新应用。
UNMETHYLATED CpG dinucleotides are more frequent in the genomes of bacteria and viruses than of vertebrates. We report here that bacterial DNA and synthetic oligodeoxynucleotides containing unmethylated CPG dinucleotides induce murine B cells to proliferate and secrete immunoglobulin in vitro and in vivo. This activation is enhanced by simultaneous signals delivered through the antigen receptor. Optimal B-cell activation requires a DNA motif in which an unmethylated CpG dinucleotide is flanked by two 5' purines and two 3' py,rimidines. Oligodeoxynucleotides containing this CpG motif induce more than 95% of all spleen B cells to enter the cell cycle. These data suggest a possible evolutionary link between immune defence based on the recognition of microbial DNA and the phenomenon of CpG suppression' in vertebrates. The potent immune activation by CpG oligonucleotides has implications for the design and interpretation of studies using 'antisense' oligonucleotides and points to possible new applications as adjuvants.