Lipoxin A4 decreases human memory B cell antibody production via an ALX/FPR2-dependent mechanism: A link between resolution signals and adaptive immunity

摘要

SummarySpecialized proresolving mediators (SPMs) are endogenous bioactive lipid molecules that play a fundamental role in the regulation of inflammation and its resolution. SPMs are classified into lipoxins, resolvins, protectins and maresins. Lipoxins and other SPMs have been identified in important immunological tissues including bone marrow, spleen and blood. Lipoxins regulate functions of the innate immune system including the promotion of monocyte recruitment and increase macrophage phagocytosis of apoptotic neutrophils. A major knowledge gap is whether lipoxins influence adaptive immune cells. Here, we analyzed the actions of lipoxin A4 (LXA4) and its receptor ALX/FPR2 on human B cells. LXA4 decreased IgM and IgG production on activated B cells through ALX/FPR2-dependent signaling, which downregulated NF-κB p65 nuclear translocation. LXA4 also inhibited human memory B cell antibody production and proliferation, but not naïve B cell function. Lastly, LXA4 decreased antigen-specific antibody production in vivo. To our knowledge, this is the first description of the actions of lipoxins on human B cells, which shows a link between resolution signals and adaptive immunity. Regulating antibody production is crucial to prevent unwanted inflammation. Harnessing the ability of lipoxins to decrease memory B cell antibody production can be beneficial to threat inflammatory and autoimmune disorders.