Lipoxin A4 decreases human memory B cell antibody production via an ALX/FPR2-dependent mechanism: A link between resolution signals and adaptive immunity (P5151)

Abstract

Abstract Specialized 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 SPM have been identified in immunological tissues including bone marrow, spleen and blood. Lipoxins regulate functions of the innate immune system such as monocyte recruitment and inhibition of neutrophil infiltration to the site of inflammation. A major knowledge gap is whether lipoxins influence adaptive immune cells. Here, we discovered that B cells express the lipoxin A4 (LXA4) receptor, ALX/FPR2, and upregulate its expression following mitogen activation. Furthermore, LXA4 decreased IgM and IgG production on activated B cells through an ALX/FPR2-dependent mechanism. This caused a reduction in NF-κB p65 nuclear translocation. We found that memory B cells express higher levels of ALX/FPR2 compared to naïve B cells. Interestingly, LXA4 inhibited human memory B cell antibody production and proliferation, but not naïve B cell function. LXA4 also decreased antigen-specific antibody production in vivo. To our knowledge, this is the first description of the effects of lipoxins on B cells, which provides a link between resolution signals and adaptive immunity. The ability of lipoxins to decrease memory B cell antibody production could be particularly beneficial to threat chronic inflammatory diseases and autoimmune disorders.