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dc.contributor.authorAllan, Lenka L.en_US
dc.contributor.authorSherr, David H.en_US
dc.date.accessioned2011-12-29T22:49:47Z
dc.date.available2011-12-29T22:49:47Z
dc.date.copyright2010
dc.date.issued2010-3-24
dc.identifier.citationAllan, Lenka L, David H Sherr. "Disruption of human plasma cell differentiation by an environmental polycyclic aromatic hydrocarbon: a mechanistic immunotoxicological study" Environmental Health 9:15. (2010)
dc.identifier.issn1476-069X
dc.identifier.urihttps://hdl.handle.net/2144/2615
dc.description.abstractBACKGROUND: The AhR is a ligand-activated transcription factor that mediates immunosuppression induced by environmental PAH and HAH. Recently, a critical role for the AhR in development of T cells involved in autoimmunity (Th17 and Treg) has been demonstrated, supporting the hypothesis that the AhR plays a key role in immune regulation both in the presence and absence of environmental ligands. Despite these results with T cells systems, little is known of the role that the AhR plays in B cell development. We have demonstrated that B cell activation with CD40 ligand, a stimulus that models adaptive immunity, induces AhR expression in primary human B cells, suggesting that activation may increase human B cell sensitivity to AhR ligands and that the AhR may play a role in B cell development. METHODS: To test these possibilities, we developed an in vitro system in which activated human B cells expressing high AhR levels are induced to differentiate into plasma cells. Consequently, the effects of benzo [a]pyrene, a prototypic environmental AhR ligand, on plasma cell differentiation could be investigated and this chemical could be exploited essentially as drug probe to implicate the role of the AhR in plasma cell development. RESULTS: A previously unattainable level of B cell differentiation into plasma cells (up to 45% conversion) was observed. Benzo [a]pyrene significantly suppressed that differentiation. γ-Irradiation after an initial proliferation phase induced by CD40 ligand and immediately prior to initiation of the differentiation phase blocked cell growth but did not affect cell viability or plasma cell differentiation. B [a]P suppressed differentiation whether or not cell growth was inhibited by γ-irradiation. CONCLUSIONS: 1) Extensive proliferation is not required during the differentiation phase per se for CD40L-activated human B cells to undergo plasma cell differentiation, and 2) an environmental PAH blocks both proliferation and differentiation of AhR expressing B cells. The results uncover a new mechanism by which environmentally ubiquitous PAHs may negatively impact human B cell-mediated immunity.en_US
dc.description.sponsorshipNational Institute of Environmental Health Sciences (P42 ES07381, RO1 ES06086, PO1 ES11624)en_US
dc.language.isoen
dc.publisherBioMed Centralen_US
dc.rightsCopyright 2010 Allan and Sherr; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.en_US
dc.rights.urihttp://creativecommons.org/licenses/by/2.0
dc.titleDisruption of Human Plasma Cell Differentiation by an Environmental Polycyclic Aromatic Hydrocarbon: A Mechanistic Immunotoxicological Studyen_US
dc.typeArticleen_US
dc.identifier.doi10.1186/1476-069X-9-15
dc.identifier.pmid20334656
dc.identifier.pmcid2851679


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Copyright 2010 Allan and Sherr; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Except where otherwise noted, this item's license is described as Copyright 2010 Allan and Sherr; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.