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A Role for Interferon Regulatory Factor 4 in Receptor Editing

机译：干扰素调节因子4在受体编辑中的作用

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Receptor editing is the primary means through which B cells revise antigen receptors and maintain central tolerance. Previous studies have demonstrated that interferon regulatory factor 4 (IRF-4) and IRF-8 promote immunoglobulin light-chain rearrangement and transcription at the pre-B stage. Here, the roles of IRF-4 and -8 in receptor editing were analyzed. Our results show that secondary rearrangement was impaired in IRF-4 but not IRF-8 mutant mice, suggesting that receptor editing is defective in the absence of IRF-4. The role of IRF-4 in receptor editing was further examined in B-cell-receptor (BCR) transgenic mice. Our results show that secondary rearrangement triggered by membrane-bound antigen was defective in the IRF-4-deficient mice. Our results further reveal that the defect in secondary rearrangement is more severe at the immunoglobulin λ locus than at the κ locus, indicating that IRF-4 is more critical for the λ rearrangement. We provide evidence demonstrating that the expression of IRF-4 in immature B cells is rapidly induced by self-antigen and that the reconstitution of IRF-4 expression in the IRF-4 mutant immature B cells promotes secondary rearrangement. Thus, our studies identify IRF-4 as a nuclear effector of a BCR signaling pathway that promotes secondary rearrangement at the immature B-cell stage.
机译：受体编辑是B细胞修改抗原受体并维持中枢耐受性的主要手段。先前的研究表明，干扰素调节因子4（IRF-4）和IRF-8在B前阶段可促进免疫球蛋白轻链重排和转录。在这里，分析了IRF-4和-8在受体编辑中的作用。我们的结果表明，IRF-4受损的继发重排受损，但IRF-8突变小鼠并未受损，这表明在缺乏IRF-4的情况下受体编辑存在缺陷。在B细胞受体（BCR）转基因小鼠中进一步检查了IRF-4在受体编辑中的作用。我们的结果表明，由膜结合抗原引发的继发性重排在IRF-4缺陷小鼠中是有缺陷的。我们的结果进一步表明，免疫球蛋白λ位点的继发重排缺陷比κ位点的缺陷更严重，这表明IRF-4对于λ重排更为关键。我们提供的证据表明，自身抗原可快速诱导未成熟B细胞中IRF-4的表达，并且IRF-4突变未成熟B细胞中IRF-4表达的重构可促进继发性重排。因此，我们的研究将IRF-4识别为BCR信号通路的核效应子，该信号通路可促进未成熟B细胞阶段的次级重排。

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