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Ahr-Mediated Transcriptional Regulation Of The Human Immunoglobulin Hs1.2 Enhancer, Sydney White Jan 2022

Ahr-Mediated Transcriptional Regulation Of The Human Immunoglobulin Hs1.2 Enhancer, Sydney White

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The 3'IGHRR is thought to be responsible for the transcription of the immunoglobulin heavy chain (IGH) gene locus, which is essential for the production of antibodies. The human 3’IGHRR, which is duplicated in humans, contains the hs3, hs4, and hs1.2 enhancers. Additionally, the hs1.2 enhancer is polymorphic in humans and consists of a 53 bp invariant sequence that can be repeated one to four times. Previous experiments in a mouse and human B-cell line model have shown that the high affinity AhR ligand and environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) can induce hs1.2 enhancer activity in an AhR-dependent manner. The AhR is …


Potential Role Of Ahr In Antibody Production, Mili Bhakta Jan 2020

Potential Role Of Ahr In Antibody Production, Mili Bhakta

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Aryl hydrocarbon receptor (AhR) mediates the immunosuppressive effects of 2,3,7,8 -tetrachlorodibenzodioxin (TCDD) in murine B cells. The effects of AhR activation on the regulation of expression of human immunoglobulin isotypes (μ, γ1-4, α1-2 and ε) and Ig secretion is unclear. Our previous results using CL-01 cell-line originating from a Burkitt’s lymphoma patient, demonstrated an inhibitory effect of TCDD on IgG expression but a surprising and marked loss of IgG secretion when the AhR was knocked out by siRNA or CRISPR/Cas9 gene editing. To determine if the AhR is a critical mediator of IgG expression, current study is focused on characterizing …


The Expression Of Major Histocompatibility Class I And Major Histocompatibility Class Ii On Macrophages In The Presence Of Aryl Hydrocarbon Antagonist (Ch-223191), Caitlin Wilson Jan 2016

The Expression Of Major Histocompatibility Class I And Major Histocompatibility Class Ii On Macrophages In The Presence Of Aryl Hydrocarbon Antagonist (Ch-223191), Caitlin Wilson

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Macrophages are crucial for ridding the body of debris and foreign cells. The aryl hydrocarbon receptor (AhR) also plays a critical role in immunity. This study examined the effect of the AhR on the expression of major histocompatiability complex class I (MHCI) and MHC class II (MHCII) in two murine macrophage cell lines. This study used Raw264.7 and J774A.1 murine macrophage cell lines. The Raw264.7 cells are from male BALB/c mice while the J774A.1 cells are from female BALB/cN mice. The addition of the AhR anatagonist CH-223191 (AhRa) showed that the AhR does not significantly impact MHCI expression. However, MHCII …


Determining The Role Of The Ahr In Immunoglobulin Expression And Class Switch Recombination, Bassam Fawaz Kashgari Jan 2015

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 …


The Aryl Hydrocarbon Receptor Regulates An Essential Transcriptional Element In The Immunoglobulin Heavy Chain Gene, Michael J. Wourms Jan 2013

The Aryl Hydrocarbon Receptor Regulates An Essential Transcriptional Element In The Immunoglobulin Heavy Chain Gene, Michael J. Wourms

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2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a ubiquitous environmental contaminant that inhibits immunoglobulin (Ig) expression and Ig heavy (IgH) chain gene transcription. Transcription of the IgH gene involves several regulatory elements including the 3'lgh regulatory region (3'lghRR) which is composed of four enhancers (hs3A, hs1,2, hs4, and hs3B). Dioxin responsive elements (DRE) in the hs4 and hs1,2 enhancers of the 3lghRR that bind the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor that regulates dioxin sensitive genes suggest that the 3'lghRR may be a transcriptional target of TCDD. The current study utilized an IgA secreting mouse …


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 …


Modulation Of The 3'Igh Regulatory Region (3'Igh Rr), A Prospective In Vitro Screening Tool For Identifying Potential Immunotoxicants, Rebecca Anne Henseler Jan 2007

Modulation Of The 3'Igh Regulatory Region (3'Igh Rr), A Prospective In Vitro Screening Tool For Identifying Potential Immunotoxicants, Rebecca Anne Henseler

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The immune system is critical to human survival. However, assessing alterations of immune function by potential immunotoxicants is complicated by the diffuse nature of the immune system, which is composed of various effector cells each with differing effector functions. Current immunotoxicity testing is limited to animal studies. We have developed a model, which may provide an in vitro alternative to animal studies in identifying immunotoxicants that specifically target B cell function (i.e., alteration of immunoglobulin (Ig) or expression and antibody secretion). This model consists of a well-characterized B cell line, CH12.LX, which appears to appropriately model primary B cell function. …