期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 44, 期 2, 页码 357-369出版社
WILEY-BLACKWELL
DOI: 10.1002/eji.201343316
关键词
Antibodies; B cells; Human; Lipoxin; Memory responses
类别
资金
- NIH [AI103690, GM038765, T90 DE021985]
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 A(4) (LXA(4)) and its receptor ALX/FPR2 on human and mouse B cells. LXA(4) decreased IgM and IgG production on activated human B cells through ALX/FPR2-dependent signaling, which downregulated NF-B p65 nuclear translocation. LXA(4) also inhibited human memory B-cell antibody production and proliferation, but not naive B-cell function. Lastly, LXA(4) 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.
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