In the spleen, the numbers of MZB cells, expressed as a percentag

In the spleen, the numbers of MZB cells, expressed as a percentage of total B cells, were significantly lower in mice on the high-fat diet (Table 1). There were no significant differences in the plasma levels of total IgM or IgM against CuOx-LDL and MDA-LDL between mice on the high-fat and control diets (Table 1). To assess the humoral innate response, mice that had been on the diets for 3 months were immunized with Pneumovax. The IgM response was similar to the response in control mice on RGFP966 C57BL/6 mice used in the immunization

experiment with db/db mice. Although there was a slightly delayed response in the mice on the control diet, there were no differences between the two diets at 7 days after immunization (Fig. 4d), nor were there any differences in subsets of B or T cells in the spleen or in the peritoneal cavity between mice immunized with vehicle or Pneumovax (data not shown). Together with https://www.selleckchem.com/products/MDV3100.html the results in db/db mice, these findings indicate that diabetes, but not insulin resistance, is associated with a blunted humoral innate response. Because diabetes seemed to influence the function of B-1 cells in db/db mice, we continued to investigate the effects of metabolic factors on B-1 cells, B-1a

cells, B-1b cells and B-2 cells in vitro, using FACS-purified mouse peritoneal B cell subpopulations from C57BL/6 mice. Isolated B-1 cells were cultured in the presence of increasing concentrations of glucose, insulin or leptin. As we have shown earlier, cultured B-1 cells secrete low levels of IgM, and addition of a TLR agonist results in a robust increase in the release of IgM [7]. As shown in Fig. 5a, stimulation of TLR-4 with Kdo2-Lipid A induced substantially the secretion of total as well as anti-CuOx-LDL and anti-MDA-LDL IgM, but this induction was gradually diminished in the presence of increasing concentrations of glucose. When IgM levels in the supernatants were related to B-1 cell numbers Cobimetinib mw there was still a trend, although not statistically significant, towards a negative effect of glucose

for IgM against CuOx-LDL and MDA-LDL (Fig. 5b). Secretion of IgM against CuOx-LDL and MDA-LDL was also investigated in B-1a, B-1b and B-2 populations separately. As shown in Fig. 5c and d, all three cell types produced IgM directed against CuOx-LDL and MDA-LDL upon TLR stimulation. This IgM secretion was inhibited by glucose in all three cell types, shown most consistently in B-1a cells (Fig. 5c and d), and accompanied by decreased cell numbers (data not shown). There was no effect of an equal concentration of mannitol, ruling out the possibility that the effect of glucose was due to osmotic stress (Fig. 5a–d). Culture of B-1 cells in the presence of increasing concentrations of insulin or leptin did not affect TLR-4-induced IgM secretion (data not shown). Together, these results indicate that high glucose concentrations have a negative impact on the activation of B-1 cells.

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