Essential requirement for polypyrimidine tract binding proteins 1 and 3 in the maturation and maintenance of mature B cells in mice,European Journal of Immunology

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Essential requirement for polypyrimidine tract binding proteins 1 and 3 in the maturation and maintenance of mature B cells in mice
European Journal of Immunology ( IF 4.5 ) Pub Date : 2021-07-02 , DOI: 10.1002/eji.202149257
Elisa Monzón-Casanova _{1,

2} , Kirsty J Bates ₁ , Christopher W J Smith ₂ , Martin Turner ₁

Affiliation

The maturation of immature B cells and the survival of mature B cells is stringently controlled to maintain a diverse repertoire of antibody specificities while avoiding self-reactivity. At the molecular level this is regulated by signaling from membrane Ig and the BAFF-receptor that sustain a pro-survival program of gene expression. Whether and how posttranscriptional mechanisms contribute to B cell maturation and survival remains poorly understood. Here, we show that the polypyrimidine tract binding proteins (PTBP) PTBP1 and PTBP3 bind to a large and overlapping set of transcripts in B cells. Both PTBP1 and PTBP3 bind to introns and exons where they are predicted to regulate alternative splicing. Moreover, they also show high-density of binding to 3’ untranslated regions suggesting they influence the transcriptome in diverse ways. We show that PTBP1 and PTBP3 are required in B cells beyond the immature cell stage to sustain transitional B cells and the B1, marginal zone and follicular B cell lineages. Therefore, PTBP1 and PTBP3 promote the maturation of quiescent B cells by regulating gene expression at the posttranscriptional level.

中文翻译：

小鼠成熟 B 细胞成熟和维持过程中多聚嘧啶束结合蛋白 1 和 3 的基本要求

未成熟 B 细胞的成熟和成熟 B 细胞的存活受到严格控制，以维持抗体特异性的多样性，同时避免自身反应。在分子水平上，这是由膜 Ig 和 BAFF 受体的信号调节的，维持基因表达的促生存程序。转录后机制是否以及如何促进 B 细胞成熟和存活仍知之甚少。在这里，我们发现多嘧啶束结合蛋白 (PTBP) PTBP1 和 PTBP3 与 B 细胞中大量重叠的转录本结合。 PTBP1 和 PTBP3 均与内含子和外显子结合，预计它们会调节选择性剪接。此外，它们还表现出与 3' 非翻译区域的高密度结合，表明它们以多种方式影响转录组。我们发现，未成熟细胞阶段之后的 B 细胞需要 PTBP1 和 PTBP3 来维持过渡 B 细胞以及 B1、边缘区和滤泡 B 细胞谱系。因此，PTBP1和PTBP3通过在转录后水平调节基因表达来促进静止B细胞的成熟。

更新日期：2021-09-01

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