The tumor promoter and NF-κB modulator Bcl-3 regulates splenic B cell development.
The tumor promoter and NF-κB modulator Bcl-3 regulates splenic B cell development.
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DOI：
10.4049/jimmunol.1300611
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发表时间：
2013-12-15
期刊：
影响因子：
--
通讯作者：
Siebenlist U
中科院分区：
文献类型：
--
作者：
Zhang X;Paun A;Claudio E;Wang H;Siebenlist U
Bcl-3是IκB蛋白家族的非典型成员。与经典成员不同，Bcl-3作为核转录辅因子发挥功能，根据上下文，可以通过与p50/NF-κB1或p52/NF-κB2同源二聚体的结合来促进或抑制基因。Bcl-3也是一种致癌基因，因为它是B细胞肿瘤中复发性易位的伴侣，导致表达失调。然而，Bcl-3的功能仍然知之甚少。我们已经研究了Bcl-3在B细胞中的作用，并发现了以前未知的参与这些细胞的脾发育。B细胞中Bcl-3的缺失导致显著更多的边缘区（MZ）和更少的滤泡（FO）B细胞。相反，在B细胞中转基因表达Bcl-3产生更少的MZ和更多的FO B细胞。与野生型细胞相比，Bcl-3−/− FO和MZ B细胞对LPS刺激的反应更强，包括增殖增加。相比之下，Bcl-3−/− FO B细胞在B细胞受体（BCR）刺激下更容易发生凋亡，也限制了它们的扩增。数据揭示Bcl-3作为B细胞命运决定的调节剂，限制MZ途径并有利于FO途径，至少部分地通过增加后者的信号特异性存活，这是与其致瘤活性相关的发现。
Bcl-3 is an atypical member of the family of IκB proteins. Unlike the classic members, Bcl-3 functions as a nuclear transcriptional cofactor that may, depending on context, promote or suppress genes via association with p50/NF-κB1 or p52/NF-κB2 homodimers. Bcl-3 is also an oncogene, since it is a partner in recurrent translocations in B cell tumors, resulting in deregulated expression. Bcl-3’s functions, however, remain poorly understood. We have investigated Bcl-3’s role in B cells and discovered a previously unknown involvement in the splenic development of these cells. Loss of Bcl-3 in B cells resulted in significantly more marginal zone (MZ) and fewer follicular (FO) B cells. Conversely, transgenic expression of Bcl-3 in B cells generated fewer MZ and more FO B cells. Both Bcl-3−/− FO and MZ B cells were more responsive to LPS stimulation compared with their wild-type counterparts, including increased proliferation. By contrast, Bcl-3−/− FO B cells were more prone to apoptosis upon B cell receptor (BCR) stimulation, also limiting their expansion. The data reveal Bcl-3 as a regulator of B cell fate determination, restricting the MZ path and favoring the FO pathway, at least in part via increased signal-specific survival of the latter, a finding of relevance to its tumorigenic activity.
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影响因子：
37.3
作者：
Maldonado V;Melendez-Zajgla J
通讯作者：
Melendez-Zajgla J
影响因子：
3.1
作者：
Ibrahim, Hazem A. H.;Amen, Furrat;Naresh, Kikkeri N.
通讯作者：
Naresh, Kikkeri N.
DOI：
10.1084/jem.20070318
发表时间：
2007-10-29
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hövelmeyer N;Wunderlich FT;Massoumi R;Jakobsen CG;Song J;Wörns MA;Merkwirth C;Kovalenko A;Aumailley M;Strand D;Brüning JC;Galle PR;Wallach D;Fässler R;Waisman A
通讯作者：
Waisman A
影响因子：
20.3
作者：
Meyer-Bahlburg A;Becker-Herman S;Humblet-Baron S;Khim S;Weber M;Bouma G;Thrasher AJ;Batista FD;Rawlings DJ
通讯作者：
Rawlings DJ
影响因子：
5.3
作者：
Keutgens, Aurore;Shostak, Kateryna;Chariot, Alain
通讯作者：
Chariot, Alain