Quantifying the impact of PFOA Exposure on B cell development and antibody production.

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 five-fold increase in metabolic markers in response to stimulation in PFOA-exposed groups compared to 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.