The aryl hydrocarbon receptor controls cell-fate decisions in B cells
AuthorVaidyanathan, B; Chaudhry, A; Yewdell, WT; Angeletti, D; Yen, W-F; Wheatley, AK; Bradfield, CA; McDermott, AB; Yewdell, JW; Rudensky, AY; ...
Source TitleJournal of Experimental Medicine
PublisherROCKEFELLER UNIV PRESS
University of Melbourne Author/sWheatley, Adam
AffiliationMicrobiology and Immunology
Document TypeJournal Article
CitationsVaidyanathan, 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. (2017). The aryl hydrocarbon receptor controls cell-fate decisions in B cells. JOURNAL OF EXPERIMENTAL MEDICINE, 214 (1), pp.197-208. https://doi.org/10.1084/jem.20160789.
Access StatusOpen Access
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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