Age effects on mouse and human B cells
Age effects on mouse and human B cells
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DOI：
10.1007/s12026-013-8440-9
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发表时间：
2013-12-01
影响因子：
4.4
通讯作者：
Frasca, Daniela
中科院分区：
文献类型：
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作者：
Blomberg, Bonnie B.;Frasca, Daniela
我们的实验室在B细胞受体（BCR）和前BCR基因鉴定和转录领域做出了贡献，并在过去的15年中专注于小鼠和人类免疫系统老化的问题。我们已经发现了老年小鼠和人类B细胞功能下降的生物标志物。这些包括免疫球蛋白（IG）类别转换（例如，IgM至IgG），酶AID（活化诱导的胞苷脱氨酶）减少和转录因子E47减少。由于磷酸-MAP激酶和磷酸-TTP（三曲脯氨酸）减少，老年B细胞中E47 mRNA稳定性降低。炎症，例如，随着年龄增长而增加的TNF-α通过增加它们的TNF-α和NF-κ B直接影响B细胞，并导致上述途径减少。在老年人对流感疫苗的反应中，类别转换和亲和力成熟都降低，我们发现的生物标志物（转换的记忆B细胞的数量和百分比以及培养物中刺激的B细胞中的AID）可以预测对疫苗的有益或降低的免疫反应。目前和未来的途径，以提高老年人的体液免疫反应进行了讨论。
Our laboratory has contributed to the areas of B cell receptor (BCR) and pre-BCR gene identification and transcription and has focused on the problem of the aged immune system in mice and humans for the last 15 years. We have found biomarkers for the decrease in B cell function in aged mice and humans. These include decreases in immunoglobulin (Ig) class switch (e.g., IgM to IgG), decreases in the enzyme AID (activation-induced cytidine deaminase) and decreases in the transcription factor E47. The E47 mRNA stability is decreased in old B cells due to decreased phospho-MAPKinase and phospho-TTP (tristetraprolin). Inflammation, e.g., TNF-alpha, which increases with age, impacts B cells directly by increasing their TNF-alpha and NF-kappa B and leads to the above decreased pathway. Both class switch and affinity maturation are decreased in elderly responses to the influenza vaccine and biomarkers we have found (numbers and percentages of switched memory B cells and AID in stimulated B cells in culture) can predict a beneficial or decreased immune response to the vaccine. Current and future avenues to improve the humoral immune response in the elderly are discussed.