Quantifying the impact of PFOA exposure on B-cell development and antibody production

• Published in: Toxicological sciences Vol. 194; no. 1; pp. 101 - 108
• Main Authors: Taylor, Krystal D, Woodlief, Tracey L, Ahmed, Aya, Hu, Qing, Duncker, Patrick C, DeWitt, Jamie C
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 28.06.2023
• Subjects: Alkanesulfonic Acids - toxicity; Animals; Antibody Formation; Caprylates - toxicity; Environmental Pollutants - toxicity; Female; Fluorocarbons - toxicity; Immunotoxicology; Male; Mice; Mice, Inbred C57BL; immunotoxicity; B cells; immunometabolism; PFAS; PFOA
• ISSN: 1096-6080; 1096-0929
• DOI: 10.1093/toxsci/kfad043

Abstract 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.