Requirement of cytokines for augmentation of the antigen-specific antibody responses by ascorbate in cultured murine T-cell-depleted splenocytes.
To gain a better understanding of the possible mechanisms by which a stable form of ascorbate, ascorbic acid 2-glucoside (AA-2G), as an ascorbate source, augments antibody responses, we examined whether AA-2G enhances the anti-sheep-red-blood-cell (SRBC) plaque-forming cell (PFC) responses elicited with distinct interleukins that provide signals for B-cell proliferation and differentiation in cultured murine T-cell-depleted splenocytes. The anti-SRBC PFC responses were markedly reduced by T-cell depletion; and additions of the concanavalin A-stimulated murine splenocytes supernatant (CAS) or interleukin (IL)-1beta, IL-2, IL-5, IL-4 or IL-6 to the culture limitedly restored the immune responses. AA-2G synergistically stimulated the anti-SRBC PFC responses in the presence of IL-1beta-, IL-2, IL-5 or CAS, IL-1beta among these cytokines being most highly affected. However, it failed to enhance the PFC responses elicited by IL-4 or IL-6. Repeated additions of ascorbic acid (AsA) during experimental periods could also produced the enhancing effect, but a single addition of the vitamin did not, because of its instability in the medium. It was shown that exposure to IL-1beta, IL-2 or IL-5 must be done at early times after antigen stimulation of the cells to support their optimal responses and that AsA exerted its effect on day 2 and day 3 after the start of culture. These results suggest that AsA may up-regulate the in vitro IgM antibody responses in a cytokine-dependent manner.
Mitsuzumi
H
H
Department of Immunochemistry, Faculty of Pharmaceutical Sciences, Okayama University, Japan.
Kusamiya
M
M
Kurimoto
T
T
Yamamoto
I
I
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects* / Q000276:immunology; D000921:Antibody-Producing Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D000941:Antigens / Q000276:immunology*; D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D006462:Hemolytic Plaque Technique; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D015848:Interleukin-5 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D012756:Sheep; D013154:Spleen / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D013997:Time Factors
D000941:Antigens; D017077:Culture Media, Conditioned; D016207:Cytokines; D016166:Free Radical Scavengers; D007375:Interleukin-1; D007376:Interleukin-2; D015848:Interleukin-5; D015850:Interleukin-6; D003208:Concanavalin A; D015847:Interleukin-4; C065378:ascorbic acid 2-O-glucoside; D001205:Ascorbic Acid