Promotion of IL-4- and IL-5-dependent differentiation of anti-μ-primed B cells by ascorbic acid 2-glucoside

Abstract

The stable ascorbic acid derivative 2-O-alpha-D-glucopyranosyl-L-ascorbic acid (AA-2G) was used to investigate the role of ascorbic acid (AA) in B cell differentiation in vitro. AA-2G is stable in a solution unlike AA but is hydrolyzed by cellular alpha-glucosidase to release AA. Mouse spleen B cells were primed for 2 days with an anti-mu antibody in the presence of interleukin (IL)-4 and IL-5 and then washed and recultured with AA-2G in the presence of IL-4 and IL-5. AA-2G, but not AA, dose-dependently increased IgM production, the greatest enhancement being 150% at concentrations of more than 0.5mM. In the absence of IL-4 and IL-5, primed B cells produced a negligible amount of IgM, and AA-2G had no effect. AA-2G-induced IgM production in the presence of IL-4 and IL-5 was inhibited by the alpha-glucosidase inhibitor castanospermine. Intracellular AA content, depleted during the priming period, increased by adding AA-2G at the start of reculture. Treatment of B cells with AA-2G resulted in an increase in the number of IgM-secreting cells, CD138-positive cells and CD45R/B220-negative cells. The number of viable cells in untreated cultures decreased gradually, but the decrease was significantly attenuated by AA-2G, resulting in about 70% more viable cells in AA-2G-treated cultures. AA-2G caused a slight but reproducible enhancement of DNA synthesis and a slight decrease in the number of cells with a sub-G1 DNA content. These results demonstrated that AA released from AA-2G enhanced cytokine-dependent IgM production in anti-mu-primed B cells and suggest that its effect is caused through promoting the differentiation of B cells to plasma cells and attenuating the gradual decrease in the number of viable cells.

Ascorbic acid synthesis and transportation capacity in old laying hens and the effects of dietary supplementation with ascorbic acid

“…The spleen plays vital roles in the immune systems of old laying hens because of the age-related involution of the thymus [ 31 ]. It has been documented that AA can promote the differentiation of B cells and IgM production [ 32 ], scavenge free radicals produced by macrophages during the bacteria-fighting process [ 33 ], and accelerate the maturation of T lymphocytes [ 34 ]. Thus, the increases in the AA and DHA concentrations in the spleen resulting from dietary AA supplementation might contribute to the elevated CD4 + T lymphocyte numbers and the increased anti-BSA IgG concentrations in the sera of the 78-week-old laying hens.…”

Stability, transdermal penetration, and cutaneous effects of ascorbic acid and its derivatives

“…32 In contrast to AA-Pal, the stable AA derivative AA-2G 25 6 is hydrolyzed by cellular a-glucosidase to release AA. 33 Topically applied AA-2G has also been shown to exhibit the physiological effects of AA. 34,35 AA-2G does penetrate the skin, 22 but the rate of penetration and in vivo conversion to AA has not yet been determined.…”

“…In contrast to AA‐Pal, the stable AA derivative AA‐2G 6 is hydrolyzed by cellular α‐glucosidase to release AA . Topically applied AA‐2G has also been shown to exhibit the physiological effects of AA .…”

Anti-Allergic Activity of Monoacylated Ascorbic Acid 2-Glucosides

“…2- O -α- d -Glucopyranosyl- l -ascorbic acid (AA-2G, Figure 1 ) is one of the stable ascorbate derivatives [ 6 ]. AA-2G shows vitamin C activity after enzymatic hydrolysis to AA by α-glucosidase, that is, AA-2G is a pro-vitamin C agent [ 7 , 8 , 9 , 10 ]. AA-2G has been permitted by the Japanese Government as a quasi-drug and food additive, and it is being used as a medical additive in the field of cosmetics.…”