Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are
bioactive n-3 polyunsaturated fatty acids (PUFAs) in fish oil that
exert immunomodulatory effects. The general paradigm suggests n-3
PUFAs 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
antigen presentation. The functional changes n-3 PUFAs exert on B
cells were determined and compared to dendritic cells (DC).
Initially, we established n-3 PUFAs increased cytokine production
from lipopolysaccharide (LPS) stimulated B cells ex vivo relative to
the control. In contrast, n-3 PUFAs decreased DC activation with LPS
by reducing cytokine secretion and decreasing surface expression of
costimulatory molecules. The antigen presentation assays revealed n-3 PUFAs decreased IL-2 secretion from CD4 p+ T cells when B cells
presented antigen compared to the control. In comparison, only CD69
surface expression on CD4 p+ T cells decreased when n-3 PUFA
treated DCs presented the antigen compared to the control.
Mechanistically, we investigated changes in lipid microdomain
clustering on B cells and DCs induced by n-3 PUFAs to determine if
the 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
clinically relevant EPA and DHA ethyl esters on antibody production
in an obese murine model. EPA and DHA differentially increased ex
vivo B-cell activation, in vivo natural serum IgM and cecal IgA
compared to controls. Altogether, the data show n-3 PUFAs boost
immune responses from B cells, which challenges the current notion
about n-3 PUFAs, and has clinical implications for immunocompromised populations, such as the obese.Ph.D