title: Lipoxin A₄ modulates adaptive immunity by decreasing memory B-cell responses via an ALX/FPR2-dependent mechanism.
abstract: Specialized proresolving mediators are endogenous bioactive lipid molecules that play a fundamental role in the regulation of inflammation and its resolution. Lipoxins and other specialized proresolving mediators 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 and mouse B cells. LXA₄ decreased IgM and IgG production on activated human 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 an OVA immunization mouse model. To our knowledge, this is the first description of the actions of lipoxins on human B cells, demonstrating 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.
authors.forename: Sesquile
authors.initials: S
authors.lastname: Ramon
authors.forename: Simona
authors.initials: S
authors.lastname: Bancos
authors.forename: Charles N
authors.initials: CN
authors.lastname: Serhan
authors.forename: Richard P
authors.initials: RP
authors.lastname: Phipps
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology*; D000818:Animals; D000906:Antibodies / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D015536:Down-Regulation / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology*; D007249:Inflammation / Q000276:immunology; D044045:Lipoxins / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D021381:Protein Transport / Q000276:immunology; D044042:Receptors, Formyl Peptide / Q000276:immunology*; D044067:Receptors, Lipoxin / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000906:Antibodies; C105101:FPR2 protein, human; C442142:HSH2D protein, human; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D044045:Lipoxins; D044042:Receptors, Formyl Peptide; D044067:Receptors, Lipoxin; C040527:lipoxin A4