The aryl hydrocarbon receptor controls cell-fate decisions in B cells Journal Article
| Authors: | Vaidyanathan, B.; Chaudhry, A.; Yewdell, W. T.; Angeletti, D.; Yen, W. F.; Wheatley, A. K.; Bradfield, C. A.; McDermott, A. B.; Yewdell, J. W.; Rudensky, A. Y.; Chaudhuri, J. |
| Article Title: | The aryl hydrocarbon receptor controls cell-fate decisions in B cells |
| Abstract: | 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. |
| Journal Title: | Journal of Experimental Medicine |
| Volume: | 214 |
| Issue: | 1 |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Date Published: | 2017-01-01 |
| Start Page: | 197 |
| End Page: | 208 |
| Language: | English |
| DOI: | 10.1084/jem.20160789 |
| PROVIDER: | scopus |
| PMCID: | PMC5206498 |
| PUBMED: | 28011866 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 February 2017 -- Source: Scopus |
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