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ARID5B influences B cell development and function in mouse.
Haematologica ( IF 10.1 ) Pub Date : 2022-08-04 , DOI: 10.3324/haematol.2022.281157
Charnise Goodings 1 , Xujie Zhao 1 , Shannon McKinney-Freeman 2 , Hui Zhang 3 , Jun J Yang 4
Affiliation  

There is growing evidence for an inherited basis of susceptibility to childhood acute lymphoblastic leukemia (ALL). Genome-wide association studies by us and others have identified non-coding ALL risk variants at the ARID5B gene locus, but the molecular mechanisms linking ARID5B to normal and malignant hematopoiesis remain largely unknown. Using a Vav1-driven transgenic mouse model, we characterized the role of Arid5b in hematopoiesis in vivo. Arid5b overexpression resulted in a dramatic reduction in the proportion of circulating B cells, immature, and mature B-cell fractions in the peripheral blood and the bone marrow, and also decrease of follicular B cells in the spleen. There were significant defects in Bcell activation upon Arid5b overexpression in vitro with hyperactivation of the B-cell receptor signaling at baseline. In addition, increased mitochondrial oxygen consumption rate of naïve or stimulated B cells of Arid5bOE mice was observed, compared to wildtype counterparts. Taken together, our results indicate that ARID5B may play important role in B-cell development and function.

中文翻译:

ARID5B 影响小鼠 B 细胞的发育和功能。

越来越多的证据表明儿童急性淋巴细胞白血病 (ALL) 具有遗传易感性。我们和其他人进行的全基因组关联研究已经确定了 ARID5B 基因位点的非编码 ALL 风险变异,但将 ARID5B 与正常和恶性造血联系起来的分子机制仍然很大程度上未知。使用 Vav1 驱动的转基因小鼠模型,我们描述了 Arid5b 在体内造血中的作用。Arid5b 过表达导致外周血和骨髓中循环 B 细胞、未成熟和成熟 B 细胞部分的比例显着降低,以及脾脏中滤泡 B 细胞的减少。在体外 Arid5b 过表达时 B 细胞活化存在显着缺陷,基线时 B 细胞受体信号传导过度活化。此外,与野生型对应物相比,观察到 Arid5bOE 小鼠的幼稚或刺激 B 细胞的线粒体耗氧率增加。总之,我们的结果表明 ARID5B 可能在 B 细胞发育和功能中发挥重要作用。
更新日期:2022-08-04
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