NK cells in the CD19- B220+ bone marrow fraction are increased in senescence and reduce E2A and surrogate light chain proteins in B cell precursors.
NK cells in the CD19- B220+ bone marrow fraction are increased in senescence and reduce E2A and surrogate light chain proteins in B cell precursors.
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DOI：
10.1016/j.mad.2009.03.002
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发表时间：
2009-06
影响因子：
5.3
通讯作者：
Riley RL
中科院分区：
文献类型：
--
作者：
King AM;Keating P;Prabhu A;Blomberg BB;Riley RL
E2 A编码的蛋白质是B谱系特化和定型的关键转录调节因子，已显示在老年时B细胞前体减少。E2 A调节编码替代轻链蛋白λ5和VpreB的基因。在老年，B细胞前体表达较少的替代轻链，这导致前B细胞受体功能受损和衰老中新前B细胞的扩增减少。在此，我们表明，老年骨髓增加了哈代A级分（CD 19- B220+）细胞，包括NK细胞，可以抑制E47（E2 A）蛋白和替代轻链蛋白在B细胞前体中的表达。在体外，NK对E47蛋白的相关抑制作用不依赖于接触，并可通过中和TNFα部分逆转。在体内，通过抗脱唾液酸GM 1抗体处理耗尽老年小鼠的NK细胞，导致替代轻链蛋白水平恢复到年轻B细胞前体的典型水平。这些研究表明，NK细胞，在CD 19- B220+骨髓细胞部分，可能有助于骨髓微环境，有可能负调控E47（E2 A）以及替代轻链水平的B细胞前体在老年。
E2A-encoded proteins, key transcriptional regulators in B lineage specification and commitment, have been shown to decrease in B cell precursors in old age. E2A regulates genes encoding the surrogate light chain proteins λ5 and VpreB. In old age, B cell precursors express less surrogate light chain and this results in compromised pre-B cell receptor function and diminished expansion of new pre-B cells in senescence. Herein, we show that aged bone marrow has increased Hardy Fraction A (CD19- B220+) cells, including NK cells, that can inhibit both E47 (E2A) protein and surrogate light chain protein expression in B cell precursors. In vitro, NK associated inhibition of E47 protein is contact independent and partially reversed by neutralization of TNFα. In vivo, depletion of NK cells in aged mice by treatment with anti-asialo GM1 antibody led to restoration of surrogate light chain protein levels to that typical of young B cell precursors. These studies suggest that NK cells, within the CD19- B220+ bone marrow cell fraction, may contribute to a bone marrow microenvironment that has the potential to negatively regulate E47 (E2A) as well as surrogate light chain levels in B cell precursors in old age.
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影响因子：
5.3
作者：
Sherwood, EM;Xu, W;Riley, RL
通讯作者：
Riley, RL
DOI：
10.1084/jem.188.4.699
发表时间：
1998-08-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kee BL;Murre C
通讯作者：
Murre C
鼠骨髓中B220+细胞的亚群不会表达CD19，并且包含天然杀伤细胞的祖细胞。
影响因子：
15.3
作者：
Rolink, A;tenBoekel, E;Melchers, F;Fearon, DT;Krop, I;Andersson, J
通讯作者：
Andersson, J
影响因子：
4.3
作者：
Fernandez, S;Knopf, MA;McGillis, JP
通讯作者：
McGillis, JP
DOI：
10.4049/jimmunol.182.1.138
发表时间：
2009-01-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Alter-Wolf S;Blomberg BB;Riley RL
通讯作者：
Riley RL