XBP1, downstream of Blimp-1, expands the secretory apparatus and other organelles, and increases protein synthesis in plasma cell differentiation

XBP1, downstream of Blimp-1, expands the secretory apparatus and other organelles, and increases protein synthesis in plasma cell differentiation
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DOI:
10.1016/j.immuni.2004.06.010
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发表时间:
2004-07-01
期刊:
影响因子:
32.4
通讯作者:
Staudt, LM
Staudt, LM
中科院分区:
医学1区
文献类型:
--
作者:
Shaffer, AL;Shapiro-Shelef, M;Staudt, LM

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B细胞分化为免疫球蛋白分泌浆细胞的分化由两个转录因子Blimp-1和XBP1控制。通过基因表达分析,我们定义了一组基因,其在小鼠浆细胞分化过程中的诱导取决于Blimp-1和/或XBP1。 Blimp-1缺陷B细胞无法上调大多数浆细胞特异性基因,包括XBP1。 XBP1缺陷的B细胞通常诱导Blimp-1,但未能上调编码许多分泌途径成分的基因。相反,XBP1的异位表达诱导了广泛的分泌途径基因,并在物理上扩展了内质网。另外,XBP1增加了细胞大小,溶酶体含量,线粒体质量和功能,核糖体数量和总蛋白质合成。因此,XBP1协调细胞结构和功能的各种变化,从而导致专业分泌细胞的特征表型。
The differentiation of B cells into immunoglobulin-secreting plasma cells is controlled by two transcription factors, Blimp-1 and XBP1. By gene expression profiling, we defined a set of genes whose induction during mouse plasmacytic differentiation is dependent on Blimp-1 and/or XBP1. Blimp-1-deficient B cells failed to upregulate most plasma cell-specific genes, including xbp1. Differentiating xbp1-deficient B cells induced Blimp-1 normally but failed to upregulate genes encoding many secretory pathway components. Conversely, ectopic expression of XBP1 induced a wide spectrum of secretory pathway genes and physically expanded the endoplasmic reticulum. In addition, XBP1 increased cell size, lysosome content, mitochondrial mass and function, ribosome numbers, and total protein synthesis. Thus, XBP1 coordinates diverse changes in cellular structure and function resulting in the characteristic phenotype of professional secretory cells.