Aryl Hydrocarbon Receptor deficiency influences B cell response. Mus musculus

The aryl hydrocarbon receptor (AhR), a transcription factor known for mediating xenobiotic toxicity, is expressed in B cells, which are known targets for environmental pollutants. However, it is unclear what the physiological functions of AhR in B cells are. We show here that expression of Ahr in B cells is up-regulated upon B cell receptor (BCR) engagement and IL-4 treatment. Addition of a natural ligand of AhR, FICZ, induces AhR translocation to the nucleus and transcription of the AhR target gene Cyp1a1, showing that the AhR pathway is functional in B cells. AhR-deficient (Ahr-/-) B cells proliferate less than AhR-sufficient (Ahr+/+) cells following in vitro BCR stimulation and in vivo adoptive transfer models confirmed that Ahr-/- B cells are outcompeted by Ahr+/+ cells. Transcriptome comparison of AhR-deficient and sufficient B cells identified cyclin O (Ccno), a direct target of AhR, as a top candidate affected by AhR deficiency. Overall design: Total RNA obtained from in vitro activated AhR sufficient and AhR deficient B cells

芳基烃受体（aryl hydrocarbon receptor, AhR）是一种已知可介导外源性毒物毒性的转录因子，在B细胞中表达，而B细胞是环境污染物的已知靶标。然而，目前尚不清楚AhR在B细胞中发挥何种生理功能。本研究证实，B细胞中Ahr基因的表达在B细胞受体（B cell receptor, BCR）活化及白细胞介素4（IL-4）处理后会上调。AhR的天然配体FICZ可诱导AhR发生核转位，并上调AhR靶基因Cyp1a1的转录，表明B细胞中AhR通路具有功能活性。体外经BCR刺激后，AhR缺陷型（Ahr-/-）B细胞的增殖能力弱于AhR功能正常型（Ahr+/+）B细胞；体内过继转移模型实验进一步证实，Ahr-/- B细胞的竞争力弱于Ahr+/+ B细胞。对AhR缺陷型与功能正常型B细胞进行转录组比较分析，发现周期蛋白O（cyclin O, Ccno）作为AhR的直接靶标，是受AhR缺失影响的核心候选基因之一。实验整体设计：从体外活化的AhR功能正常型与AhR缺陷型B细胞中提取总RNA。