Publication Date
2014
Document Type
Thesis
Committee Members
Nancy J. Bigley (Committee Member), Barbara E. Hull (Committee Member), Courtney E.W. Sulentic (Advisor)
Degree Name
Master of Science (MS)
Abstract
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent environmental toxin known to inhibit immunoglobulin (Ig) gene expression in various animal studies. We have identified the mouse 3'Ig heavy chain regulatory region (3'IgH RR) as a sensitive transcriptional target of TCDD, which may mediate the inhibitory effect of TCDD on Ig expression. Interestingly, the human hs1,2 enhancer is polymorphic and has been associated with a number of autoimmune diseases.
Suggesting a species difference, TCDD inhibited mouse hs1,2 enhancer activation and activated basal human hs1,2 (hs-hs1,2) enhancer activity in the mouse B-cell line. The objective of this study was to elucidate the effects of TCDD on the polymorphic human hs1,2 enhancer using a human B-cell line (CL-01) and luciferase reporter constructs regulated by each of the human hs1,2 alleles. Our results verify that TCDD alone activates each of the hu-hs1,2 alleles.
Surprisingly, B-cell stimulation through the Toll-like receptors (TLR) 7, 8, and 9, and the AhR antagonist inhibited basal activity of the hu-hs1,2 alleles and TCDD co-treatment reversed TLR-induced inhibition. Contrary to this, TLR stimulates IgM secretion as well as class switching to IgG secretion. These results suggest that the hu-hs1,2 enhancer may be a negative regulator of 3'IgH RR activity and Ig expression.
Page Count
65
Department or Program
Microbiology and Immunology
Year Degree Awarded
2014
Copyright
Copyright 2014, some rights reserved. My ETD may be copied and distributed only for non-commercial purposes and may be modified only if the modified version is distributed with these same permissions. All use must give me credit as the original author.
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 License.
