A B-cell subset uniquely responsive to innate stimuli accumulates in aged mice
A B-cell subset uniquely responsive to innate stimuli accumulates in aged mice
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DOI：
10.1182/blood-2011-01-330530
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发表时间：
2011-08-04
期刊：
影响因子：
20.3
通讯作者：
Cancro, Michael P.
中科院分区：
文献类型：
--
作者：
Hao, Yi;O'Neill, Patrick;Cancro, Michael P.
我们发现了一个独特的成熟B细胞亚群，它会随着年龄的增长而积累，我们将其称为年龄相关的B细胞。到22个月时，这些细胞包含高达30%的成熟B细胞。尽管与其他成熟B细胞亚群共享一些特征，但它们对BCR和CD 40刺激是难治的。相反，它们响应于TLR 9或TLR 7刺激，并在BCR和TLR结合时最大化分裂，导致IG产生和IL-10和IL-4的优先分泌。尽管在B淋巴细胞刺激因子（BLyS）受体表达和BLyS结合能力方面与滤泡B细胞相似，但这些细胞不依赖BLyS存活。它们既不是循环，也不是老化BM中固有改变的B淋巴细胞生成的结果，而是似乎是由在个体一生中耗尽性扩增的成熟B细胞产生的。最后，它们有效地呈现Ag，并有利于极化到TH 17轮廓。总而言之，这些发现表明，虽然成熟的原代B细胞生态位的大小随着年龄的增长而保持不变，但它越来越多地被对BCR驱动的激活不敏感但对先天受体刺激有反应的细胞所占据。（血。2011; 118（5）：1294-1304）
We have discovered a distinct mature B-cell subset that accumulates with age, which we have termed age-associated B cells. These cells comprise up to 30% of mature B cells by 22 months. Despite sharing some features with other mature B-cell subsets, they are refractory to BCR and CD40 stimulation. Instead, they respond to TLR9 or TLR7 stimulation and divide maximally on combined BCR and TLR ligation, leading to Ig production and preferential secretion of IL-10 and IL-4. Although similar to follicular B cells in both B-lymphocyte stimulator (BLyS) receptor expression and BLyS binding capacity, these cells do not rely on BLyS for survival. They are neither cycling nor the result of intrinsically altered B lymphopoiesis in aged BM, but instead appear to be generated from mature B cells that exhaustively expand during the individual's lifetime. Finally, they present Ag effectively and favor polarization to a TH17 profile. Together, these findings reveal that while the magnitude of the mature primary B-cell niche is maintained with age, it is increasingly occupied by cells refractory to BCR-driven activation yet responsive to innate receptor stimulation. (Blood. 2011; 118(5):1294-1304)