乘客5人
淋巴细胞生成
B细胞
细胞分化
生物
转录因子
重组激活基因
细胞生物学
乙酰化
谱系(遗传)
祖细胞
癌症研究
干细胞
基因
免疫学
遗传学
抗体
重组
作者
Andrés Gámez-García,María Espinosa-Alcantud,Alberto Bueno-Costa,Elisenda Alari‐Pahissa,Anna Marazuela-Duque,Joshua K. Thackray,Chandni Ray,Clara Berenguer,Poonam Kumari,Joan Josep Bech‐Serra,Thomas Braun,Alessandro Ianni,Jay A. Tischfield,Lourdes Serrano,Manel Esteller,José Luis Sardina,Carolina de la Torre,Mikael Sigvardsson,Berta N. Vazquez,Alejandro Vaquero
标识
DOI:10.1038/s41590-024-01995-7
摘要
Abstract B lymphopoiesis is orchestrated by lineage-specific transcription factors. In B cell progenitors, lineage commitment is mediated by Pax5, which is commonly mutated in B cell acute lymphoblastic leukemia. Despite its essential role in immunity, the mechanisms regulating Pax5 function remain largely unknown. Here, we found that the NAD + -dependent enzyme SIRT7 coordinates B cell development through deacetylation of Pax5 at K198, which promotes Pax5 protein stability and transcriptional activity. Neither Pax5 K198 deacetylated nor acetylated mimics rescued B cell differentiation in Pax5 −/− pro-B cells, suggesting that B cell development requires Pax5 dynamic deacetylation. The Pax5 K198 deacetylation mimic restored lineage commitment in Pax5 −/− pro-B cells and B cell differentiation in Sirt7 −/− pro-B cells, suggesting the uncoupling of differentiation from lineage commitment. The SIRT7–Pax5 interplay was conserved in B cell acute lymphoblastic leukemia, where SIRT7 expression correlated with good prognosis. Our findings reveal a crucial mechanism for B lymphopoiesis and highlight the relevance of sirtuins in immune function.
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