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Quantifying the impact of PFOA exposure on B-cell development and antibody production
Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals; the vast majority are environmentally and biologically persistent, and some have demonstrated toxicity, including cancer, effects on metabolism, endocrine disruption, and immune dysfunction. Suppression of T-cell-dependent antibody...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Oxford University Press
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10306397/ https://www.ncbi.nlm.nih.gov/pubmed/37162486 http://dx.doi.org/10.1093/toxsci/kfad043 |
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author | Taylor, Krystal D Woodlief, Tracey L Ahmed, Aya Hu, Qing Duncker, Patrick C DeWitt, Jamie C |
author_facet | Taylor, Krystal D Woodlief, Tracey L Ahmed, Aya Hu, Qing Duncker, Patrick C DeWitt, Jamie C |
author_sort | Taylor, Krystal D |
collection | PubMed |
description | Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals; the vast majority are environmentally and biologically persistent, and some have demonstrated toxicity, including cancer, effects on metabolism, endocrine disruption, and immune dysfunction. Suppression of T-cell-dependent antibody responses (TDAR) has been observed in numerous studies of PFAS but mechanisms remain elusive. Evidence from our work suggests that B cells and how they use energy are impacted by PFAS exposure. We hypothesize that a well-studied and immunotoxic PFAS, perfluorooctanoic acid (PFOA), alters B-cell subclasses and markers of their metabolism. Adult male and female C57BL/6 mice were given PFOA (0 or 7.5 mg/kg) via gavage for 15 days, a duration and dose sufficient to suppress the TDAR. After dosing and immunization of subgroups, spleens were prepared to quantify B-cell subsets. Flow cytometric analysis revealed decreased numbers of plasmablasts, follicular, naïve, and overall B-cell subclasses in female PFOA-exposed groups. Male PFOA-exposed groups had a significant increase in follicular B cells and other subsets had decreases, including in the overall number of B cells. Twenty-four hours after naïve B-cell isolation and ex vivo activation, metabolic measurements revealed a 5-fold increase in metabolic markers in response to stimulation in PFOA-exposed groups compared with controls. These findings suggest that B-cell development and survival may be hindered by PFOA exposure, but that activation of the remaining B cells was not. Based on these findings, PFOA-mediated suppression of the primary IgM antibody response results changes to specific subsets of B cells. |
format | Online Article Text |
id | pubmed-10306397 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-103063972023-06-29 Quantifying the impact of PFOA exposure on B-cell development and antibody production Taylor, Krystal D Woodlief, Tracey L Ahmed, Aya Hu, Qing Duncker, Patrick C DeWitt, Jamie C Toxicol Sci Immunotoxicology Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals; the vast majority are environmentally and biologically persistent, and some have demonstrated toxicity, including cancer, effects on metabolism, endocrine disruption, and immune dysfunction. Suppression of T-cell-dependent antibody responses (TDAR) has been observed in numerous studies of PFAS but mechanisms remain elusive. Evidence from our work suggests that B cells and how they use energy are impacted by PFAS exposure. We hypothesize that a well-studied and immunotoxic PFAS, perfluorooctanoic acid (PFOA), alters B-cell subclasses and markers of their metabolism. Adult male and female C57BL/6 mice were given PFOA (0 or 7.5 mg/kg) via gavage for 15 days, a duration and dose sufficient to suppress the TDAR. After dosing and immunization of subgroups, spleens were prepared to quantify B-cell subsets. Flow cytometric analysis revealed decreased numbers of plasmablasts, follicular, naïve, and overall B-cell subclasses in female PFOA-exposed groups. Male PFOA-exposed groups had a significant increase in follicular B cells and other subsets had decreases, including in the overall number of B cells. Twenty-four hours after naïve B-cell isolation and ex vivo activation, metabolic measurements revealed a 5-fold increase in metabolic markers in response to stimulation in PFOA-exposed groups compared with controls. These findings suggest that B-cell development and survival may be hindered by PFOA exposure, but that activation of the remaining B cells was not. Based on these findings, PFOA-mediated suppression of the primary IgM antibody response results changes to specific subsets of B cells. Oxford University Press 2023-05-10 /pmc/articles/PMC10306397/ /pubmed/37162486 http://dx.doi.org/10.1093/toxsci/kfad043 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of the Society of Toxicology. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Immunotoxicology Taylor, Krystal D Woodlief, Tracey L Ahmed, Aya Hu, Qing Duncker, Patrick C DeWitt, Jamie C Quantifying the impact of PFOA exposure on B-cell development and antibody production |
title | Quantifying the impact of PFOA exposure on B-cell development and antibody production |
title_full | Quantifying the impact of PFOA exposure on B-cell development and antibody production |
title_fullStr | Quantifying the impact of PFOA exposure on B-cell development and antibody production |
title_full_unstemmed | Quantifying the impact of PFOA exposure on B-cell development and antibody production |
title_short | Quantifying the impact of PFOA exposure on B-cell development and antibody production |
title_sort | quantifying the impact of pfoa exposure on b-cell development and antibody production |
topic | Immunotoxicology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10306397/ https://www.ncbi.nlm.nih.gov/pubmed/37162486 http://dx.doi.org/10.1093/toxsci/kfad043 |
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