Specialized proresolution mediators enhance human B cell differentiation to antibody secreting cells (53.10)

Abstract

Abstract The resolution of inflammation is an active and dynamic process critical in maintaining homeostasis. Newly identified lipid-derived mediators are key players during the process of inflammation resolution. These specialized proresolution mediators (SPM) constitute separate classes of compounds, which include lipoxins, resolvins, protectins and maresins, all derived from essential fatty acids. SPM regulate aspects of the immune response, including inhibition of neutrophil infiltration, reduction of T cell cytokine production and stimulation of macrophage phagocytic activity. However, their effects on B lymphocytes are unknown. Our study shows that the novel SPM 17-hydroxydosahexaenoic acid (17-HDHA), resolvin D1 (RvD1) but not protectin D1 (PD1), strongly increase the ability of normal human B cells to produce IgM and IgG. The increased antibody levels are due to an increased number of antibody-secreting cells. Furthermore, SPM regulate the expression of the transcription factors Blimp-1, Xbp-1 and Pax-5, and promote B cell differentiation towards a CD27+CD38+ antibody secreting cell phenotype. None of the SPM affect proliferation and are non-toxic. The increase in plasma cell differentiation and antibody production coincides with the known involvement of SPM during the late stages of inflammation and pathogen clearance. These new findings highlight the potential applications of SPM as endogenous and non-toxic adjuvants and anti-inflammatory therapeutic molecules.