The resolution of inflammation is an active and dynamic process critical in maintaining homeostasis. Newly identified lipid mediators have been recognized as key players during the resolution phase. These specialized proresolving mediators (SPM) constitute separate families that include lipoxins, resolvins, protectins, and maresins, each derived from essential polyunsaturated fatty acids. New results demonstrate that SPM regulate aspects of the immune response, including reduction of neutrophil infiltration, decreased T cell cytokine production, and stimulation of macrophage phagocytic activity. The actions of SPM on B lymphocytes remain unknown. Our study shows that the novel SPM 17-hydroxydosahexaenoic acid (17-HDHA), resolvin D1, and protectin D1 are present in the spleen. Interestingly, 17-HDHA and resolvin D1, but not protectin D1, strongly increase activated human B cell IgM and IgG production. Furthermore, increased Ab production by 17-HDHA is due to augmented B cell differentiation toward a CD27+ CD38+ Ab-secreting cell phenotype. The 17-HDHA did not affect proliferation and was nontoxic to cells. Increase of plasma cell differentiation and Ab production supports the involvement of SPM during the late stages of inflammation and pathogen clearance. The present study provides new evidence for SPM activity in the humoral response. These new findings highlight the potential applications of SPM as endogenous and nontoxic adjuvants, and as anti-inflammatory therapeutic molecules.