EPA and DHA do not exert equivalent effects on B lymphocyte plasma membrane organization: Implications for developing biomarkers of fish oil for targeting B cell immunity

Abstract

We have established that fish oil, enriched in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), can regulate the function of B cells. Specifically, we reported that fish oil exerts immunomodulatory effects on B cell antigen presentation and lipopolysaccharide induced activation. We have also discovered that the functional changes in response to fish oil are accompanied by a disruption in the clustering of signaling lipid microdomains known as lipid rafts, a potential biomarker for B cell activity. Therefore, we first determined the dose of fish oil that serves to disrupt B cell lipid rafts. Administration of fish oil at the human equivalent of 4 grams and above per day (currently used pharmacologically) disrupted raft clustering, which correlated with changes in function. We then determined which fatty acid in fish oil was responsible for disrupting rafts by feeding mice diets enriched either in EPA or DHA. B cells isolated from mice consuming the DHA‐enriched but not the EPA‐enriched diet had diminished raft clustering. Supporting studies in cell culture and in liposomes revealed the same effect. Altogether, our data suggest that DHA is more potent than EPA in disrupting the B cell plasma membrane, which has implications for biomarker development and ultimately the design of fish oil formulations for targeting B cell function.Grant Funding Source: NIH R15AT006122 (to S.R.S.) and NIH R03CA162427 (to J.F.)