An intact NF-κB signaling pathway is required for maintenance of mature B cell subsets
An intact NF-κB signaling pathway is required for maintenance of mature B cell subsets
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DOI：
10.1016/s0161-5890(99)00031-0
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发表时间：
1999-02-01
影响因子：
3.6
通讯作者：
Oltz, EM
中科院分区：
文献类型：
--
作者：
Bendall, HH;Sikes, ML;Oltz, EM
NF-κ B/Rel转录因子家族成员在B细胞发育过程中组成型表达，并进一步被有丝分裂原激活诱导。在单个NF-κ B亚基中携带生殖系破坏的小鼠表现出B淋巴细胞活化和存活的明显缺陷。然而，NF-κ B在B细胞亚群的产生和维持中的作用在这些敲除动物中由于其他免疫细胞的功能损伤而难以剖析。为了直接解决体液免疫区室中NF-κ B的细胞自主需求，产生了在B谱系细胞中表达I κ B α的反式显性形式的转基因小鼠。尽管抑制剂的表达对基础或LPS诱导的NF-κ B水平仅具有适度的影响，但转基因B细胞对响应于B细胞受体（BCR）交联的细胞增殖和NF-κ B诱导显著受损。此外，反式显性抑制剂产生了剂量依赖性减少的人口中的成熟脾B细胞。这种细胞缺陷在再循环到成人骨髓的长寿B淋巴细胞亚群中更为明显。总之，这些结果表明，BCR介导的信号传导必须维持NF-κ B水平高于严格的阈值，以适当调节B细胞稳态。(C)1999爱思唯尔科技有限公司。保留所有权利。
Members of the NF-kappa B/Rel transcription factor family are expressed constitutively during B cell development and are further induced by mitogen activation. Mice harboring germline disruptions in individual NF-kappa B subunits exhibit distinct defects in B lymphocyte activation and survival. However, the role of NF-kappa B in the production and maintenance of B cell subsets has been difficult to dissect in these knockout animals due to functional impairment of other immune cells. To directly address the cell autonomous requirements for NF-kappa B in humoral immune compartments, transgenic mice were generated that express a trans-dominant form of I kappa B alpha in B lineage cells. Whereas expression of the inhibitor had only modest effects on basal or LPS-induced levels of NF-kappa B, transgenic B cells were significantly impaired for cellular proliferation and NF-kappa B induction in response to B cell receptor (BCR) crosslinking. Furthermore, the trans-dominant inhibitor produced a dose-dependent reduction in the population of mature splenic B cells. This cellular defect was more pronounced in long-lived B lymphocyte subsets that recirculate to the adult bone marrow. Together, these results indicate that BCR-mediated signaling must maintain NF-kappa B levels above a stringent threshold for proper regulation of B cell homeostasis. (C) 1999 Elsevier Science Ltd. All rights reserved.