Graded expression of interferon regulatory factor-4 coordinates isotype switching with plasma cell differentiation
Graded expression of interferon regulatory factor-4 coordinates isotype switching with plasma cell differentiation
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DOI：
10.1016/j.immuni.2006.07.009
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发表时间：
2006-08-01
期刊：
影响因子：
32.4
通讯作者：
Singh, Harinder
中科院分区：
文献类型：
--
作者：
Sciammas, Roger;Shaffer, A. L.;Singh, Harinder
同型转换与浆细胞分化协调的分子机制还知之甚少。我们发现干扰素调节因子-4(IRF-4)通过控制分别编码AID和Blimp-1的Aicda和Prdm1基因的表达来调节这两个过程。全基因组分析表明，IRF4(-/-)B细胞不能诱导整个依赖Blimp-1的浆细胞程序。在IRF4(-/-)B细胞中恢复AID或Blimp-1表达分别促进同型转换或分泌。在分化B细胞和靶向Prdm1过程中，IRF-4呈分级表达。较高浓度的IRF-4诱导Prdm1，从而从生发中心基因表达程序过渡到浆细胞程序。我们提出了一个基因调控网络，在这个网络中，IRF-4的分级表达在发育过程中协调了同型转换与浆细胞分化。
Molecular mechanisms underlying the coordination of isotype switching with plasma cell differentiation are poorly understood. We show that interferon regulatory factor-4 (IRF-4) regulates both processes by controlling the expression of the Aicda and Prdm1 genes, which encode AID and Blimp-1, respectively. Genome-wide analysis demonstrated that Irf4(-/-) B cells failed to induce the entire Blimp-1 -dependent plasma cell program. Restoration of AID or Blimp-1 expression in Irf4(-/-) B cells promoted isotype switching or secretion, respectively. IRF-4 was expressed in a graded manner in differentiating B cells and targeted Prdm1. Higher concentration of IRF-4 induced Prdm1 and consequently the transition from a germinal center gene expression program to that of a plasma cell. We propose a gene-regulatory network in which graded expression of IRF-4 developmentally coordinates isotype switching with plasma cell differentiation.