The aryl hydrocarbon receptor controls cell-fate decisions in B cells.
The aryl hydrocarbon receptor controls cell-fate decisions in B cells.
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DOI：
10.1084/jem.20160789
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发表时间：
2017-01
期刊：
影响因子：
--
通讯作者：
Chaudhuri J
中科院分区：
文献类型：
--
作者：
Vaidyanathan B;Chaudhry A;Yewdell WT;Angeletti D;Yen WF;Wheatley AK;Bradfield CA;McDermott AB;Yewdell JW;Rudensky AY;Chaudhuri J
Vaidyanathan 等人。据报道，环境传感器芳基碳氢化合物受体在 BCR 信号下游的 B 细胞中诱导表达，并且它分别通过 aicda 和 prdm1 负调节类别转换和浆细胞分化来控制 B 细胞命运。细胞异质性的产生是适应性免疫系统的基本特征。这在体液免疫反应过程中得到了最好的例证，此时扩展的 B 细胞克隆呈现出多种细胞命运，包括类别转换的 B 细胞、分泌抗体的浆细胞和记忆 B 细胞。尽管每种细胞类型对于免疫都至关重要，但它们的生成必须受到严格控制，因为类别转换的 B 细胞无法恢复到亲本同种型，而终末分化的浆细胞无法对记忆池做出贡献。在这项研究中，我们表明环境传感器芳基碳氢化合物受体 (AhR) 在 B 细胞激活时被高度诱导，并在调节激活诱导的细胞命运结果中发挥关键作用。我们发现 AhR 通过改变激活诱导的胞苷脱氨酶表达来负向调节离体类别转换重组。我们进一步证明，AhR 在流感病毒感染和模型抗原免疫后抑制体内类别转换。此外，通过 Bach2 调节 Blimp-1 的表达，AhR 抑制 B 细胞在离体时分化为浆母细胞，在体内则抑制 B 细胞分化为分泌抗体的浆细胞。这些实验表明，AhR 作为 B 细胞中的分子变阻器来制动效应器反应，可能促进最佳回忆反应。因此，AhR 可能代表了疫苗接种期间操纵 B 细胞反应的新分子靶点。
Vaidyanathan et al. report that the environmental sensor aryl hydrocarbon receptor is inducibly expressed in B cells downstream of BCR signaling and that it controls B cell fates by negatively modulating class switching and plasma cell differentiation via aicda and prdm1, respectively. Generation of cellular heterogeneity is an essential feature of the adaptive immune system. This is best exemplified during humoral immune response when an expanding B cell clone assumes multiple cell fates, including class-switched B cells, antibody-secreting plasma cells, and memory B cells. Although each cell type is essential for immunity, their generation must be exquisitely controlled because a class-switched B cell cannot revert back to the parent isotype, and a terminally differentiated plasma cell cannot contribute to the memory pool. In this study, we show that an environmental sensor, the aryl hydrocarbon receptor (AhR) is highly induced upon B cell activation and serves a critical role in regulating activation-induced cell fate outcomes. We find that AhR negatively regulates class-switch recombination ex vivo by altering activation-induced cytidine deaminase expression. We further demonstrate that AhR suppresses class switching in vivo after influenza virus infection and immunization with model antigens. In addition, by regulating Blimp-1 expression via Bach2, AhR represses differentiation of B cells into plasmablasts ex vivo and antibody-secreting plasma cells in vivo. These experiments suggest that AhR serves as a molecular rheostat in B cells to brake the effector response, possibly to facilitate optimal recall responses. Thus, AhR might represent a novel molecular target for manipulation of B cell responses during vaccination.
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