2007;117:175C184. E47. Leptin-induced phospho-STAT3 and phospho-AMPK levels were much like those in B cells from individuals with obesity. Conclusions These results demonstrate that leptin can be responsible for decreased B cell function in obesity. response to the vaccine in both young and seniors individuals. The peak of the response Hexestrol was earlier (t7) as compared to what is usually seen (t28) because of repeated immunizations having a vaccine comprising the pandemic (p)2009 H1N1 strain for the third consecutive yr. For the same reason, almost all individuals were seroprotected at t0 (not shown). Open in a separate window Number Hexestrol 1 Obesity decreases the influenza vaccine response in young and seniors individualsSera were collected before (t0) and after vaccination (t7), and analyzed by HAI assay. To evaluate antibody production to the vaccine (and therefore to all viral strains present in the vaccine), the reciprocal of the titers after vaccination is definitely shown. The response peaked at t7 and decreased only minimally at t28. The reciprocal of the titers decreased from 196 to 160 (slim young), from 80 to 62 (young with obesity), from 56 to 51 (slim seniors) and from 28 to 23 (seniors with obesity). ANOVA: percentages of switched memory, IgM memory space, late/exhausted memory space, na?ve, transitional B cell subsets. Results in Fig. 2 display that obesity significantly decreases the percentages of switched memory space B cells (Fig. 2A) which are also reduced lean seniors as compared to lean young individuals, as we have previously reported (8, 11, 12, 13). No effect of obesity on IgM memory space B cells was observed (Fig. 2B). Obesity increases the percentages of late/exhausted memory space B cells (Fig. 2C), the pro-inflammatory B cell subset, in young individuals only, and the percentages of this subset in young individuals with obesity are comparable to those observed in all seniors individuals. Late/exhausted memory space B cells will also be significantly improved in lean seniors as compared to lean young individuals, as we have previously demonstrated (14). A small effect of obesity was observed on na?ve B cells (Fig. 2D). Transitional B cells, the anti-inflammatory B cells (Fig. 2E), are decreased in the blood of both young and Hexestrol seniors individuals with obesity as compared to slim settings. Obesity is definitely associated with an increased production of pro-inflammatory cytokines and a decreased production of anti-inflammatory cytokines in cultured B cells Not only the phenotypic composition but also the practical quality of the B cell pool influences the individuals response. We have previously shown that unstimulated B cells from seniors individuals make significantly higher levels of TNF-, measured by icTNF-, than those from young individuals, and these positively correlate with serum TNF- and negatively correlate with B cell function (8). Here, we confirmed these results and also prolonged them by showing that significantly higher percentages of unstimulated B cells from individuals with obesity make icTNF- as compared to lean settings (Fig. 3A). We also measured the production of pro- and anti-inflammatory cytokines by B cells, after activation of B cells with CpG and anti-Ig, which are ideal stimuli for IL-10 production (15). Results display that B cells from individuals with obesity make more IL-6 (Fig. 3B) and Hexestrol less IL-10 Hexestrol than slim settings (Fig. 3C). B cells from individuals with obesity support T cell swelling It has recently been shown that murine and human being B cells are essential regulators of swelling in individuals with T2D by assisting pro-inflammatory T cells (5). We wanted to check if this Raf-1 was also true in individuals with obesity. Results in Fig. 3 also display that aging decreases IL-17 and IFN- production and that the removal of B cells from PBMC cultures of young and seniors individuals significantly reduces the secretion of both IL-17 (Fig. 3D) and IFN- (Fig. 3E), suggesting that the connection between T and B cells (and perhaps monocytes) is vital for the secretion of these inflammatory cytokines. This is especially true for participants in the obese condition. Obesity is definitely associated with decreased AID and E47 in cultured B cells AID is definitely a marker of ideal.