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• W2163131928 endingPage "474" @default.
• W2163131928 startingPage "463" @default.
• W2163131928 abstract "The persistent environmental contaminant and immunotoxicant, 2,3,7,8-tetrachlorodibenzo-<i>p</i>-dioxin (TCDD), markedly suppresses humoral immune responses. We recently reported impaired down-regulation of paired box 5 (Pax5), a repressor of B cell differentiation and concomitant suppression of the IgM response by TCDD in the murine CH12.LX B cell line. The objectives of the current study were to determine the impact of TCDD treatment on molecular outcomes characteristic of terminal B cell differentiation and to assess the role that Pax5 isoforms plays in the suppression of B cell differentiation by TCDD. In this study, we show that the highly abundant full-length Pax5 isoform, Pax5a, and at least two additional modestly expressed Pax5 isoforms were expressed in CH12.LX and splenic B cells. In lipopolysaccharide (LPS)-activated B cells, all of the identified Pax5 isoforms were synchronously down-regulated, and in the presence of TCDD cotreatment they were abnormally and synchronously elevated, suggesting a common mechanism of regulation. Furthermore, B cell differentiation markers X-box protein-1 and major histocompatibility complex class II showed that the levels to which Pax5 was derepressed by TCDD were sufficient to impair B cell differentiation and immunoglobulin gene expression. Confirming the involvement of Pax5, ectopic expression of Pax5a in the LPS-activated CH12.LX cells closely mimicked the suppression of the IgM response by TCDD. In summary, our results demonstrate that Pax5a has a critical role in both the TCDD-mediated impairment of B cell differentiation and the suppression of the humoral immune response." @default.
• W2163131928 created "2016-06-24" @default.
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• W2163131928 date "2008-05-15" @default.
• W2163131928 modified "2023-10-15" @default.
• W2163131928 title "2,3,7,8-Tetrachlorodibenzo-<i>p</i>-dioxin-Mediated Impairment of B Cell Differentiation Involves Dysregulation of Paired Box 5 (Pax5) Isoform, Pax5a" @default.
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• W2163131928 doi "https://doi.org/10.1124/jpet.108.139857" @default.
• W2163131928 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2562000" @default.
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• W2163131928 hasPublicationYear "2008" @default.
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