MicroRNAs miR-155 and miR-16 Decrease AID and E47 in B Cells from Elderly Individuals.
MicroRNAs miR-155 and miR-16 Decrease AID and E47 in B Cells from Elderly Individuals.
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DOI：
10.4049/jimmunol.1500520
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发表时间：
2015-09-01
期刊：
影响因子：
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通讯作者：
Blomberg BB
中科院分区：
文献类型：
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作者：
Frasca D;Diaz A;Romero M;Ferracci F;Blomberg BB
我们在过去几年中的研究已经确定了B细胞特异性生物标志物，能够预测年轻人和老年人的最佳抗体应答。这些生物标志物是激活诱导的胞苷脱氨酶（AID），类转换重组和体细胞超突变的酶;转录因子E47，对AID表达至关重要;以及产生最佳记忆B细胞的能力。此外，我们发现老年人血清中和B细胞固有的促炎状态增加，对B细胞功能产生负面影响。我们现在已经研究了特定的炎症微RNA（miR）是否有助于老年B细胞中E47和AID的减少。我们的数据表明，E47和AID mRNA的稳定性较低的刺激B细胞从老年人。我们在来自年轻和老年个体的人未刺激的B细胞中测量了对CSR至关重要的两种miR（miR-155和miR-16）的表达，其基本原理是刺激前这些miR的增加将降低细胞活化后的E47/AID。我们发现这些miR和B细胞内在炎症在老化的未刺激的B细胞中上调，并且在用CpG刺激后在相同的B细胞中与AID呈负相关。我们认为，老年人B细胞中AID的下调可能是通过miR-155与AID mRNA的3′-UTR结合和/或miR-16与E47 mRNA的3′-UTR结合，以及在转录水平上减少E47对AID的作用。我们的研究结果表明，新的分子途径，导致降低B细胞功能与老化。
Our research in the past few years has identified B cell-specific biomarkers able to predict optimal antibody responses in both young and elderly individuals. These biomarkers are activation-induced cytidine deaminase (AID), the enzyme of class switch recombination and somatic hypermutation; the transcription factor E47, crucial for AID expression; and the ability to generate optimal memory B cells. Moreover, we have found that the increased pro-inflammatory status of the elderly, both in sera and intrinsic to B cells, negatively impacts B cell function. We have now investigated whether particular inflammatory micro-RNAs (miRs) contribute to decreased E47 and AID in aged B cells. Our data indicate that E47 and AID mRNA stability is lower in stimulated B cells from elderly individuals. We measured the expression of two miRs crucial for CSR, miR-155 and miR-16, in human unstimulated B cells from young and elderly individuals with the rationale that increases in these before stimulation would decrease E47/AID upon cell activation. We found these miRs and B-cell intrinsic inflammation up-regulated in aged unstimulated B cells and negatively associated with AID in the same B cells after stimulation with CpG. We propose that the down-regulation of AID in aged human B cells may occur through binding of miR-155 to the 3′-UTR of AID mRNA and/or binding of miR-16 to the 3′-UTR of E47 mRNA as well as at the transcriptional level of less E47 for AID. Our results indicate novel molecular pathways leading to reduced B cell function with aging.