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2,3,7,8-Tetrachlordibenzo-P-Dioxin Mediated Immune Suppression Through Interactions At The 3'Immunoglobulin Heavy Chain Regulatory Region Enhancers, David Harold Ellis Jan 2010

2,3,7,8-Tetrachlordibenzo-P-Dioxin Mediated Immune Suppression Through Interactions At The 3'Immunoglobulin Heavy Chain Regulatory Region Enhancers, David Harold Ellis

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2,3,7,8-Tetrachlordibenzo-p-dioxin (TCDD) is a potent toxin which inhibits the antibody response of B cells. The 3'IgHRR which is involved in transcriptional regulation of the heavy-chain polypeptide of antibodies is inhibited by TCDD. The hs1,2 enhancer region, isolated from the 3'IgHRR, is also inhibited while the isolated hs4 is activated by TCDD. This project sought to determine if that dichotomy in effects results from interactions at enhancer-specific binding sites for AhR, thought to mediate transcriptional effects of TCDD, and NFκB, a transcription factor involved in B cell activation. Here, I report a difference in the effect of TCDD on transcriptional activity …


The Im-9 Cell Line: A Model For Evaluating Tcdd-Induced Modulation Of The Polymorphic Human Hs1,2 Enhancer Within The 3' Immunoglobulin Heavy Chain Regulatory Region, Ruth C. Chambers-Turner Jan 2010

The Im-9 Cell Line: A Model For Evaluating Tcdd-Induced Modulation Of The Polymorphic Human Hs1,2 Enhancer Within The 3' Immunoglobulin Heavy Chain Regulatory Region, Ruth C. Chambers-Turner

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2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a disrupter, of B-cell differentiation, induces binding of the aryl hydrocarbon receptor (AhR) nuclear complex to dioxin responsive elements (DRE) within the mouse immunoglobulin heavy chain regulatory region (3'IgHRR), and produces a marked inhibition of 3'IgHRR activation, IgH expression, and antibody secretion in a well-characterized mouse B-cell line (CH12.LX). The mouse 3'IgHRR consists of at least four enhancers (hs3a; hs1,2; hs3b; hs4), and is highly homologous with the three enhancers (hs3; hs1,2; hs4) of the human 3'IgHRR. A polymorphism of the human hs1,2 enhancer (resulting in varying numbers of tandem repeats containing a DRE and κB site) has …