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Determining The Role Of The Ahr In Immunoglobulin Expression And Class Switch Recombination, Bassam Fawaz Kashgari

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The aryl hydrocarbon receptor (AhR) is a ligand-activated cytosolic transcription factor that regulates xenobiotic-metabolizing enzymes. It mediates the toxicity of various environmental chemicals such as 2,3,7,8-tetracholorodibenzo-p-dioxin (TCDD). TCDD inhibits the differentiation of B cells into antibody-secreting cells and inhibits immunoglobulin (Ig) expression in various animal models. We have previously determined that TCDD-induced inhibition of the mouse Ig heavy chain gene (mo-Igh) is AhR-dependent. This inhibition may be mediated by binding of the AhR to dioxin response elements (DREs) within the 3'Igh regulatory region (3'IghRR) and inhibition of 3'IghRR activity, a significant transcriptional regulator of Ig expression. However, there are structural …