The reduced expression of surrogate light chains in B cell precursors from senescent BALB/c mice is associated with decreased E2A proteins

The reduced expression of surrogate light chains in B cell precursors from senescent BALB/c mice is associated with decreased E2A proteins
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DOI:
10.1016/s0047-6374(00)00157-3
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发表时间:
2000-09-01
影响因子:
5.3
通讯作者:
Riley, RL
Riley, RL
中科院分区:
医学3区
文献类型:
--
作者:
Sherwood, EM;Xu, W;Riley, RL

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衰老小鼠表现出骨髓中前B细胞数量减少。在此,我们表明,分子,λ 5和VpreB,其中包括替代轻链组分的前B细胞受体,减少在pro-B/早期前B细胞在体外衍生自骨髓的18-27个月大的BALB/c小鼠用IL-7刺激后。如半定量RT-PCR所示,λ 5和VpreB表达在mRNA水平上均降低;这表明在衰老B细胞前体中观察到的替代轻链减少是由功能失调的转录调节引起的。替代轻链的转录部分受E2 A(E47)基因产物调节。在衰老的B细胞前体中,E2 A蛋白(包括E47)的水平降低高达90%。E2 A(E47)表达减少和随后替代轻链组分λ 5和VpreB转录减少可部分解释衰老中观察到的B谱系细胞产生减少。(C)2000爱思唯尔科学爱尔兰有限公司保留所有权利。
Senescent mice exhibit decreased numbers of pre-B cells in the bone marrow. Herein, we show that the molecules, lambda 5 and VpreB, which comprise the surrogate light chain component of the pre-B cell receptor, are reduced in pro-B/early pre-B cells derived in vitro from the bone marrow of 18-27 months old BALB/c mice after stimulation with IL-7. Both lambda 5 and VpreB expression were decreased at the mRNA level as indicated by semi-quantitative RT-PCR; this suggests that the reduced surrogate light chains seen in senescent B cell precursors result from dysfunctional transcriptional regulation. The transcription of surrogate light chains is regulated, in part, by E2A (E47) gene products. Levels of E2A proteins, including E47, were decreased in senescent B cell precursors by up to 90%. Reduced E2A (E47) expression and subsequent reduced transcription of the surrogate light chain components lambda 5 and VpreB may, in part, explain the diminished production of B lineage cells observed in senescence. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.