Specialized Proresolving Mediators Enhance Human B Cell Differentiation to Antibody-Secreting Cells

Abstract

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.

A randomized controlled trial of the effects of n-3 fatty acids on resolvins in chronic kidney disease

“…In a mouse model of acute kidney injury, 17-HDHA and RvD1 are generated after ischemia reperfusion injury in plasma and kidney tissue with or without DHA administration suggesting they are important in renal injury [21]. The increase in 17-HDHA may be clinically important because it can affect a number of different immune mechanisms relevant to the progression of renal disease including promotion of phagocytosis [22], suppression of the proinflammatory cytokines that mediate renal injury [23], and activating differentiation of B cells into antibody secreting cells that are important for a functional humoral immune response [24].…”

n-3 PUFAs enhance the frequency of murine B-cell subsets and restore the impairment of antibody production to a T-independent antigen in obesity

“…Gurzell et al showed that administration of a DHA enriched diet to mice on a 129 background increased fecal IgA in the absence of antigen ( 14 ). In another study, Ramon et al showed that in vitro treatment of human B cells with select resolvins enhanced IgM and IgG production ( 43 ).…”

Intravenous fish oil lipid emulsion promotes a shift toward anti-inflammatory proresolving lipid mediators

“…17-HDHA can be converted locally and is protective in mouse models of arthritis, colitis, and renal reperfusion injury (4,9,16). RvD 1 and 17-HDHA enhance the humoral immune response via an increase in activated B cell IgM and IgG production (24). Fat-1 mice with high levels of DHA and EPA have elevated concentrations of 18-HEPE and 17-HDHA (14).…”