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Environmental Toxicants And Human B Cells: Insights From Crispr Editing And Genomic Sequencing, Clayton Allex-Buckner
Environmental Toxicants And Human B Cells: Insights From Crispr Editing And Genomic Sequencing, Clayton Allex-Buckner
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The human immunoglobulin heavy chain gene locus (IGH) has two 3 prime regulatory regions (3’IGHRR), each containing three enhancers (hs3, hs1.2, hs4). In animal models, the 3’IghRR regulates IgH expression and class switch recombination (CSR) to different Ig isotypes. The 3’IGHRR hs1.2 enhancer in humans is polymorphic in that an invariant sequence (IS) can be repeated one to four times in tandem. The hs1.2 polymorphism is of interest due to its association with several human autoimmune disorders and its potential sensitivity to exogenous substances such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or dioxin). In mouse models, TCDD inhibits the hs1.2 enhancer and 3’IghRR …
Potential Role Of Ahr In Antibody Production, Mili Bhakta
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 …
Species Differences In The Effects Of Tcdd On A Transcriptional Regulatory Region Within The Ig Heavy Chain Gene, Zahra J. Alfaheeda
Species Differences In The Effects Of Tcdd On A Transcriptional Regulatory Region Within The Ig Heavy Chain Gene, Zahra J. Alfaheeda
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The immunoglobulin heavy chain gene (Igh) is regulated by numerous regulatory elements including the 3'Igh regulatory region (3'IghRR). Several transcription factors are involved in modulating the 3'IghRR including NF-B, AP-1, and the aryl hydrocarbon receptor (AhR). The AhR is a ligand-activated transcription factor that mediates the transcription of genes involved in the metabolism of environmental toxicants such as TCDD. TCDD binds AhR and regulates immunoglobulin (Ig) expression in B cells of animal models. This modulation appears to be directly mediated by binding of the AhR to dioxin response elements (DRE) within the 3'IghRR. Structural differences have been found between the …