N‐3 PUFAs reorganize B cell membrane rafts and molecular order accompanied by differential effects on B cell function

Abstract

n‐3 PUFAs manipulate lipid raft 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 a high n‐3 PUFA dose remodeled mouse B cell raft clustering. To establish relevance, we first tested a n‐3 PUFA dose modeling human intake on B cell raft organization, relative to a control, using biochemical and quantitative imaging methods. Biochemical analysis revealed incorporation of docosahexaenoic acid into phosphatidylcholines of raft‐like domains with no change in cholesterol distribution. TIRF and fluorescence polarization imaging showed n‐3 PUFAs manipulated B cell raft size, increased GM1 expression, and increased membrane order upon cross‐linking GM1 molecules. Finally, we tested the hypothesis that modifying rafts would suppress B cell responses ex vivo. Contrary to expectations, n‐3 PUFAs enhanced LPS‐induced B cell activation, yet suppressed B cell stimulation of naïve CD4+ T cells. Overall, the results demonstrated a relevant n‐3 PUFA dose remodeled rafts; furthermore, the data showed raft remodeling was accompanied by unique changes in B cell function.Grant Funding Source: NIH R15AT006122