A bistable switch underlying B-cell differentiation and its disruption by the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Toxicological Sciences : an Official Journal of the Society of Toxicology
Sudin BhattacharyaQiang Zhang

Abstract

The differentiation of B cells into antibody-secreting plasma cells upon antigen stimulation, a crucial step in the humoral immune response, is disrupted by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Several key regulatory proteins in the B-cell transcriptional network have been identified, with two coupled mutually repressive feedback loops among the three transcription factors B-cell lymphoma 6 (Bcl-6), B lymphocyte-induced maturation protein 1(Blimp-1), and paired box 5 (Pax5) forming the core of the network. However, the precise mechanisms underlying B-cell differentiation and its disruption by TCDD are not fully understood. Here we show with a computational systems biology model that coupling of the two feedback loops at the Blimp-1 node, through parallel inhibition of Blimp-1 gene activation by Bcl-6 and repression of Blimp-1 gene deactivation by Pax5, can generate a bistable switch capable of directing B cells to differentiate into plasma cells. We also use bifurcation analysis to propose that TCDD may suppress the B-cell to plasma cell differentiation process by raising the threshold dose of antigens such as lipopolysaccharide required to trigger the bistable switch. Our model further predicts that high doses of TCDD m...Continue Reading

References

Nov 1, 1994·Environmental Health Perspectives·L S Birnbaum
Apr 30, 1996·Proceedings of the National Academy of Sciences of the United States of America·M Singh, B K Birshtein
Jun 1, 1996·Trends in Genetics : TIG·W Hanna-Rose, U Hansen
Jan 1, 1996·Annual Review of Cell and Developmental Biology·J V Schmidt, C A Bradfield
Mar 1, 1997·Critical Reviews in Toxicology·J C Rowlands, J A Gustafsson
Apr 7, 1998·Immunity·M K SlifkaR Ahmed
Apr 29, 1998·Reviews on Environmental Health·B L Johnson, C DeRosa
Jun 25, 1998·Current Opinion in Immunology·M K Slifka, R Ahmed
Dec 10, 1998·International Immunology·R A ManzA Radbruch
Dec 30, 1998·Trends in Biochemical Sciences·J E Ferrell
Feb 5, 2000·Nature·T S GardnerJ J Collins
Mar 21, 2000·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·S FieringD I Martin
Jan 4, 2001·Current Opinion in Hematology·L J McHeyzer-WilliamsM G McHeyzer-Williams
Mar 10, 2001·Nature·L Chang, M Karin
Jun 23, 2001·Immunity·M HorcherM Busslinger
Jul 19, 2001·Nature·A M ReimoldL H Glimcher
Aug 23, 2001·Current Biology : CB·C P Bagowski, J E Ferrell
Nov 29, 2001·Nature Immunology·K L Calame
Dec 6, 2001·Nature Reviews. Molecular Cell Biology·J J TysonB Novak
May 4, 2002·Nature Cell Biology·Eitan Shaulian, Michael Karin
Aug 8, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Farha H VasanwalaAlexander L Dent
Nov 26, 2002·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·John J TysonBela Novak
Jan 14, 2003·Annual Review of Immunology·Kathryn L CalameChainarong Tunyaplin
Mar 14, 2003·Environmental Health Perspectives·Melvin E AndersenJames E Dennison

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Citations

Jun 25, 2010·Journal of Toxicology and Environmental Health. Part B, Critical Reviews·Qiang ZhangRory B Conolly
Oct 19, 2010·Toxicological Sciences : an Official Journal of the Society of Toxicology·Courtney E W Sulentic, Norbert E Kaminski
Jan 8, 2011·Toxicological Sciences : an Official Journal of the Society of Toxicology·Emily A McClureJay I Goodman
Apr 26, 2013·Open Biology·Qiang ZhangMelvin E Andersen
Apr 3, 2010·BMC Systems Biology·Qiang ZhangMelvin E Andersen
Oct 15, 2011·PLoS Computational Biology·Beata HatTomasz Lipniacki
Jun 11, 2014·BMC Pharmacology & Toxicology·Rentian FengXiang-Qun Xie
Aug 29, 2014·Environmental Science and Pollution Research International·Mateusz KędziorGrzegorz Terlecki
Jul 31, 2016·Toxicological Sciences : an Official Journal of the Society of Toxicology·Peter DornbosJohn J LaPres
Jan 12, 2016·PLoS Computational Biology·Akram Méndez, Luis Mendoza
Aug 15, 2014·Environmental Health Perspectives·Qiang ZhangMelvin E Andersen
Jun 5, 2015·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Troy D HubbardGary H Perdew
Sep 5, 2019·Frontiers in Immunology·Jennifer EncisoCarlos Villarreal
Jan 12, 2021·Frontiers in Cellular and Infection Microbiology·Thomas Hollin, Karine G Le Roch
Apr 13, 2019·Current Opinion in Biotechnology·Jacob D DavisEberhard O Voit
May 7, 2021·Briefings in Bioinformatics·Yan Li, Shao-Wu Zhang

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