2,3,7,8-四氯二苯并-对二恶英(TCDD)是一种持久性环境污染物,是芳香烃受体(AhR)的高亲和力配体。在动物模型中,通过TCDD的AhR激活通常抑制抗体分泌。然而,尚不清楚这是否转化为人类抗体生产。使用人Burkitt淋巴瘤B细胞系(CL-01),可以刺激分泌Ig并进行类别转换重组为其他Ig同种型,本研究评估了AhR激活或拮抗对CD40L+IL-4刺激的人Ig同种型表达谱的影响。我们的结果表明,AhR激动剂(TCDD和靛玉红)对IgM或IgA分泌几乎没有影响,这也不是由刺激引起的。然而,AhR激活显著抑制刺激诱导的IgG分泌,由AhR拮抗剂CH223191逆转的作用。Ig重链(IgH)恒定区基因表达的评估(即Cμ,编码IgM的Cγ1-4、Cα1-2和Cε,IgG1-4、IgA1-2和IgE,分别)表现出不同的效果。虽然Cμ和Cα2转录物不受刺激或AhR激动剂的影响,AhR激活显著抑制刺激诱导的Cγ2-4和CεmRNA转录本,这被AhR拮抗作用逆转了。值得注意的是,在不存在外源AhR配体的情况下的AhR拮抗作用显着增加了IgG和IgA的分泌以及Cγ2-4和Cε的表达。这些结果表明,AhR活性的调节差异地改变IgH同种型表达谱和抗体分泌,这可能部分依赖于细胞刺激。由于人为产生的各种化学物质,工业,Pharmaceutical,饮食,细菌来源结合AhR,例如,环境暴露改变AhR活性(即激活或抑制)的能力可能对免疫功能和抗体相关疾病状况具有直接影响。
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental contaminant and high affinity ligand for the aryl hydrocarbon receptor (AhR). In animal models, AhR activation by TCDD generally inhibits antibody secretion. However, it is less clear if this translates to human antibody production. Using a human Burkitt lymphoma B-cell line (CL-01) that can be stimulated to secrete Ig and undergo class switch recombination to other Ig isotypes, the current study evaluated the effects of AhR activation or antagonism on the human Ig isotypic expression profile with CD40L+IL-4 stimulation. Our results suggest that AhR agonists (TCDD and indirubin) have little to no effect on IgM or IgA secretion, which were also not induced with stimulation. However, AhR activation significantly inhibited stimulation-induced IgG secretion, an effect reversed by the AhR antagonist CH223191. Evaluation of Ig heavy chain (IgH) constant region gene expression (ie Cμ, Cγ1-4, Cα1-2, and Cε that encode for IgM, IgG1-4, IgA1-2, and IgE, respectively) demonstrated differential effects. While Cμ and Cα2 transcripts were unaffected by stimulation or AhR agonists, AhR activation significantly inhibited stimulation-induced Cγ2-4 and Cε mRNA transcripts, which was reversed by AhR antagonism. Notably, AhR antagonism in the absence of exogenous AhR ligands significantly increased IgG and IgA secretion as well as the expression of Cγ2-4 and Cε. These results suggest that modulation of AhR activity differentially alters the IgH isotypic expression profile and antibody secretion that may be partly dependent on cellular stimulation. Since a variety of chemicals from anthropogenic, industrial, pharmaceutical, dietary, and bacterial sources bind the AhR, the ability of environmental exposures to alter AhR activity (i.e. activate or inhibit) may have a direct influence on immune function and antibody-relevant disease conditions.