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Species Differences in the Effects of TCDD on a Transcriptional Regulatory Region within the Ig Heavy Chain Gene

Alfaheeda, Zahra J.
http://rave.ohiolink.edu/etdc/view?acc_num=wright1464105119

Abstract Details

2016, Master of Science (MS), Wright State University, Microbiology and Immunology.
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 human IGH and mouse Igh genes, including a duplication of the 3’IGHRR in humans and a polymorphic region in the human hs1.2 enhancer. This region is sensitive to TCCD-mediated modulation in mouse models whereas in in humans, several polymorphisms have been correlated with several autoimmune diseases. The objective of this study was to determine the transcriptional influence of human 3’IGHRR enhancer and sensitivity to TCDD. Using luciferase reporters controlled by the 3’IGHRR enhancers and cellular models including two well characterized B-cell lines: mouse CH12.LX and human CL-01. These cell lines can be induced to secrete Ig and can undergo class switch recombination. Our results suggest that, unlike mouse 3'IghRR, human 3'IGHRR is not sensitive to TCDD. Therefore, the role of this region remains to be determined.
Courtney Sulentic, Ph.D. (Advisor)
Barbara Hull , Ph.D. (Committee Member)
Nancy Bigley, Ph.D. (Committee Member)
Mauricio Di Fulvio, Ph.D. (Committee Member)
71 p.
Immunology; Pharmaceuticals; Toxicology
immunology; pharmaceuticals; toxicology

Recommended Citations

Citations

  • Alfaheeda, Z. J. (2016). Species Differences in the Effects of TCDD on a Transcriptional Regulatory Region within the Ig Heavy Chain Gene [Master's thesis, Wright State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=wright1464105119

    APA Style (7th edition)

  • Alfaheeda, Zahra. Species Differences in the Effects of TCDD on a Transcriptional Regulatory Region within the Ig Heavy Chain Gene. 2016. Wright State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=wright1464105119.

    MLA Style (8th edition)

  • Alfaheeda, Zahra. " Species Differences in the Effects of TCDD on a Transcriptional Regulatory Region within the Ig Heavy Chain Gene." Master's thesis, Wright State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=wright1464105119

    Chicago Manual of Style (17th edition)

wright1464105119
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© 2016, all rights reserved.
This open access ETD is published by Wright State University and OhioLINK.