These results, similar to the studies described above for B cells in adipose tissue, reveal a delicate balance of B cells subsets that exert positive and negative effects. One complication that is poorly studied is the impact of positive energy balance on host defence, and particularly humoral immunity [84]. Finally, we propose potential underlying mechanisms throughout the Squalamine lactate review by which B cell activity could be differentially regulated in response to high fat diets. measurements by Winer treatment of adipose Bregs with the saturated fatty acid palmitate (C16:0) increased survival of the Breg population. The rationale for studying palmitate was to model fatty acids that are released from adipose tissue in response to lipolysis and can serve as ligands for TLR-4 [70]. This was consistent with previous work to show that saturated and polyunsaturated fatty acids have differential effects on B cell and macrophage activation through TLRs [70C72]. However, it was not clear how saturated fatty acids would provide support for enhanced survival of the Breg population. Previous studies show that palmitate induces lipoapoptosis in several metabolic tissues, which Squalamine lactate has led to the hypothesis that saturated fatty acids can lead to lipotoxicity in several cell types, including macrophages [73C75]. For instance, Wen [76]. This line of evidence is supported by data showing that obese individuals have higher levels of circulating saturated fatty acids [77]. Thus, future mechanistic studies need to resolve how palmitate would enhance IL-10 secretion from B cells in the context of the fatty acid exerting lipotoxic effects. Perhaps there are differences in the metabolic response to palmitate between select B cell subsets and macrophages. While one study showed that palmitate treatment induced lipoapoptosis of murine B220+ splenic B cells, more studies are needed in this area [71]. The studies with palmitate also raise the question of what role each dietary fatty Squalamine lactate acid has on B cell activity. The diets used in many of the studies on B cells described above rely on high fat diets (60% of total kcal) that are predominately enriched in saturated and monounsaturated fatty acids. It is entirely possible that select fatty acids are promoting B cell dysfunction through the accumulation of select lipids as triglycerides, which can promote lipotoxicity. This notion is supported by a study showing that dendritic cells accumulate triglycerides in mouse models and in human cancer tissue samples [78]. Perhaps B cells can also accumulate triglycerides, which leads to changes in B cell activity. The role of B cells in co-morbidities associated with obesity Obesity is associated with a wide range of co-morbidities. Many of these have a B cell component that contributes towards the pathology. For example, obesity can increase the risk for coronary atherosclerosis [79]. As reviewed elsewhere, atherosclerotic lesions in humans and mice contain B cells and B-1a cells are atheroprotective through the production of natural IgM antibodies [80C82]. Depletion of murine B cells with anti-CD20 antibody also leads to an improvement in atherosclerosis [83]. These results, similar to the studies described above for B cells in adipose tissue, reveal a delicate balance of B cells subsets that exert positive and negative effects. One complication that is poorly studied is the impact of positive energy balance on host defence, and particularly humoral immunity [84]. Epidemiological studies have established that obese individuals are more likely to develop post-surgical infections [85,86]. Studies in rodents and humans also show that an increase in body mass index is correlated with increased susceptibility to bacterial and viral infections such as stimulation with a hapten-conjugated lipopolysaccharide (LPS) [94]. The enhancement in antibody production correlated with Rabbit Polyclonal to BMX an increase Squalamine lactate in the frequency of select B cell subsets. Similarly, n-3 PUFAs as ethyl esters modestly increased natural IgM and fecal IgA in diet-induced obesity, again correlating with an increased frequency of B-2 cell subsets [95]. These findings were consistent with work to show that n-3 PUFAs enhanced LPS-driven cytokine secretion from B220+ splenic B cells in lean and obese C57BL/6 and colitis-prone SMAD3?/? mice [71,96,97]. In addition, a recent murine study demonstrated that n-3 PUFAs enhanced the frequency of B-1 cells and increased antigen-specific IgM levels in a mouse model of peritonitis but had no influence on the B-2 response [71,96C98]. Altogether, dietary n-3 PUFAs may have the potential to enhance B cell-mediated immunity in diet-induced obesity. However, it remains unclear if this would ultimately have a beneficial effect, notably on B cells in the adipose tissue that are regulating insulin and glucose sensitivity. As described above, the role.