The anti-apoptotic activities of Rel and RelA required during B-cell maturation involve the regulation of Bcl-2 expression
The anti-apoptotic activities of Rel and RelA required during B-cell maturation involve the regulation of Bcl-2 expression
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DOI：
10.1093/emboj/19.23.6351
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发表时间：
2000-12-01
期刊：
影响因子：
11.4
通讯作者：
Gerondakis, S
中科院分区：
文献类型：
--
作者：
Grossmann, M;O'Reilly, LA;Gerondakis, S
Rel和RelA分别与淋巴细胞生成有关，在活化的B和T细胞中发挥独特的功能。在这里，他们在淋巴细胞发育中的联合作用，在嵌合小鼠与c-rel（-/-）rela（-/-）胎肝造血干细胞再填充检查。移植双突变细胞的小鼠缺乏成熟的IgM（lo）IgD（hi）B细胞，外周血CD 4+和CD 8 + T细胞的数量显著减少。成熟B细胞的缺乏与存活受损相关，这与bcl-2和A1表达减少一致。bcl-2转基因表达不仅阻止了细胞凋亡和增加了外周B细胞数量，而且还诱导进一步成熟为IgM（lo）IgD（hi）表型。相反，双突变T细胞的存活是正常的，bcl-2转基因不能纠正外周T细胞缺陷。这些发现表明，Rel和RelA在B-和T-细胞成熟的后期抗原非依赖性阶段发挥重要的（尽管是冗余的）功能，这些转录因子部分地通过上调Bcl-2促进外周B细胞的存活。
Rel and RelA, individually dispensable for lymphopoiesis, serve unique functions in activated B and T cells. Here their combined roles in lymphocyte development were examined in chimeric mice repopulated with c-rel(-/-) rela(-/-) fetal liver hemopoietic stem cells. Mice engrafted with double-mutant cells lacked mature IgM(lo)IgD(hi) B cells, and numbers of peripheral CD4+ and CD8+ T cells were markedly reduced. The absence of mature B cells was associated with impaired survival that coincided with reduced expression of bcl-2 and A1. bcl-2 transgene expression not only prevented apoptosis and increased peripheral B-cell numbers, but also induced further maturation to an IgM(lo)IgD(hi) phenotype. In contrast, the survival of double-mutant T cells was normal and the bcl-2 transgene could not rectify the peripheral T-cell: deficit. These findings indicate that Rel and RelA serve essential, albeit redundant, functions during the later antigen-independent stages of B- and T-cell maturation, with these transcription factors promoting the survival of peripheral B cells in part by upregulating Bcl-2.