Fish oil increases raft size and membrane order of B cells accompanied by differential effects on function

• Published in: Journal of lipid research Vol. 53; no. 4; pp. 674 - 685
• Main Authors: Rockett, Benjamin Drew, Teague, Heather, Harris, Mitchel, Melton, Mark, Williams, Justin, Wassall, Stephen R., Shaikh, Saame Raza
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2012; The American Society for Biochemistry and Molecular Biology; Elsevier
• Subjects: Animals; antigen-presenting cell; B-Lymphocytes - chemistry; B-Lymphocytes - drug effects; Biochemical analysis; Body Weight; CD4 antigen; CD4-Positive T-Lymphocytes - chemistry; CD4-Positive T-Lymphocytes - drug effects; Cell activation; Cells, Cultured; Cross-Linking Reagents - chemistry; cytokines; detergent resistant membrane; Detergents - pharmacology; Docosahexaenoic acid; Docosahexaenoic Acids - pharmacology; Eicosapentaenoic acid; Eicosapentaenoic Acid - pharmacology; Fish oils; Fish Oils - pharmacology; G(M1) Ganglioside - chemistry; imaging; Lecithin; Lipid rafts; Lipopolysaccharides - pharmacology; Lymphocyte Activation; lymphocytes; Lymphocytes B; Lymphocytes T; Macrophages; Male; Membrane Microdomains - chemistry; Membrane Microdomains - drug effects; Mice; Mice, Inbred C57BL; phosphatidylethanolamine; Phosphatidylethanolamines - chemistry; cytokines; detergent resistant membrane; lymphocytes; antigen-presenting cell; docosahexaenoic acid
• ISSN: 0022-2275; 1539-7262
• DOI: 10.1194/jlr.M021782

Fish oil (FO) targets lipid microdomain organization to suppress T-cell and macrophage function; however, little is known about this relationship with B cells, especially at the animal level. We previously established that a high FO dose diminished mouse B-cell lipid raft microdomain clustering induced by cross-linking GM1. To establish relevance, here we tested a FO dose modeling human intake on B-cell raft organization relative to a control. Biochemical analysis revealed more docosahexaenoic acid (DHA) incorporated into phosphatidylcholines than phosphatidylethanolamines of detergent-resistant membranes, consistent with supporting studies with model membranes. Subsequent imaging experiments demonstrated that FO increased raft size, GM1 expression, and membrane order upon cross-linking GM1 relative to no cross-linking. Comparative in vitro studies showed some biochemical differences from in vivo measurements but overall revealed that DHA, but not eicosapentaenoic acid (EPA), increased membrane order. Finally, we tested the hypothesis that disrupting rafts with FO would suppress B-cell responses ex vivo. FO enhanced LPS-induced B-cell activation but suppressed B-cell stimulation of transgenic naive CD4+ T cells. Altogether, our studies with B cells support an emerging model that FO increases raft size and membrane order accompanied by functional changes; furthermore, the results highlight differences in EPA and DHA bioactivity.