N-3 polyunsaturated fatty acids differentially enhance B-cell\r\nmediated immunity in lean and obese mice

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

Heather L. Teague (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

Abstract: Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are\r\nbioactive n-3 polyunsaturated fatty acids (PUFAs) in fish oil that\r\nexert immunomodulatory effects. The general paradigm suggests n-3\r\nPUFAs exert immunosuppressive effects, however, the role of n-3 PUFAs on B-cell mediated immunity is understudied. We first tested the hypothesis that n-3 PUFAs would suppress B-cell activation and\r\nantigen presentation. The functional changes n-3 PUFAs exert on B\r\ncells were determined and compared to dendritic cells (DC).\r\nInitially, we established n-3 PUFAs increased cytokine production\r\nfrom lipopolysaccharide (LPS) stimulated B cells ex vivo relative to\r\nthe control. In contrast, n-3 PUFAs decreased DC activation with LPS\r\nby reducing cytokine secretion and decreasing surface expression of\r\ncostimulatory molecules. The antigen presentation assays revealed n-3 PUFAs decreased IL-2 secretion from CD4 p+ T cells when B cells\r\npresented antigen compared to the control. In comparison, only CD69\r\nsurface expression on CD4 p+ T cells decreased when n-3 PUFA\r\ntreated DCs presented the antigen compared to the control.\r\nMechanistically, we investigated changes in lipid microdomain\r\nclustering on B cells and DCs induced by n-3 PUFAs to determine if\r\nthe observed functional changes correlated with membrane changes. N-3 PUFAs diminished lipid microdomain clustering on the B-cell surface, but had no effect on DCs. We then relied on a lean and obese murine model to determine if the functional enhancement of B cells observed ex vivo were recapitulated in vivo. N-3 PUFAs increased serum IgM levels compared to controls when stimulated by a T-independent antigen. Additionally, n-3 PUFAs supplemented to an obesogenic diet rescued the decrement in serum IgM levels observed with the obesogenic diet compared to the lean control. Considering the limitations of fish oil, we investigated the effects of the\r\nclinically relevant EPA and DHA ethyl esters on antibody production\r\nin an obese murine model. EPA and DHA differentially increased ex\r\nvivo B-cell activation, in vivo natural serum IgM and cecal IgA\r\ncompared to controls. Altogether, the data show n-3 PUFAs boost\r\nimmune responses from B cells, which challenges the current notion\r\nabout n-3 PUFAs, and has clinical implications for immunocompromised populations, such as the obese.

Additional Information

Publication

Dissertation

Language: English

Date: 2023

Subjects

Chemistry, Biochemistry;B cells;Docosahexaenoic Acids;Eicosapentaenoic Acid;High fat diet;Immunity;N-3 polyunsaturated fatty acids;Biochemistry

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