| First Author | Vaidyanathan B | Year | 2017 |
| Journal | J Exp Med | Volume | 214 |
| Issue | 1 | Pages | 197-208 |
| PubMed ID | 28011866 | Mgi Jnum | J:238773 |
| Mgi Id | MGI:5824147 | Doi | 10.1084/jem.20160789 |
| Citation | Vaidyanathan B, et al. (2017) The aryl hydrocarbon receptor controls cell-fate decisions in B cells. J Exp Med 214(1):197-208 |
| abstractText | 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. |
