N-3 polyunsaturated fatty acids modulate B cell activity in pre-clinical models: Implications for the immune response to infections

Abstract

B cell antigen presentation, cytokine production, and antibody production are targets of pharmacological intervention in inflammatory and infectious diseases. Here we review recent pre-clinical evidence demonstrating that pharmacologically relevant levels of n-3 polyunsaturated fatty acids (PUFA) derived from marine fish oils influence key aspects of B cell function through multiple mechanisms. N-3 PUFAs modestly diminish B cell mediated stimulation of classically defined naïve CD4+ Th1 cells through the major histocompatibility complex (MHC) class II pathway. This is consistent with existing data showing that n-3 PUFAs suppress the activation of Th1/Th17 cells through direct effects on helper T cells and indirect effects on antigen presenting cells. Mechanistically, n-3 PUFAs lower antigen presentation and T cell signaling by disrupting the formation of lipid microdomains within the immunological synapse. We then review data to show that n-3 PUFAs boost B cell activation and antibody production in the absence and presence of antigen stimulation. This has potential benefits for several clinical populations such as the aged and obese that have poor humoral immunity. The mode of action by which n-3 PUFA boost B cell activation and antibody production remains unclear, but may involve Th2 cytokines, enhanced production of specialized proresolving lipid mediators, and targeting of protein lateral organization in lipid microdomains. Finally, we highlight evidence to show that different n-3 PUFAs are not biologically equivalent, which has implications for the development of future interventions to target B cell activity.