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  • Title: Ganglioside GQ1b enhances anti-double-stranded DNA antibody and IgG production of PBMCs from patients with systemic lupus erythematosus.
    Author: Kanda N, Watanabe S.
    Journal: J Allergy Clin Immunol; 2000 Mar; 105(3):532-40. PubMed ID: 10719304.
    Abstract:
    BACKGROUND: Previously, we reported that ganglioside GQ1b greatly enhanced spontaneous immunoglobulin production in vitro by PBMCs from normal human subjects. OBJECTIVE: We examined in vitro effects of GQ1b on anti-double-stranded DNA (anti-dsDNA) antibody production by PBMCs from patients with systemic lupus erythematosus (SLE). METHODS: PBMCs from patients with SLE were cultured with GQ1b. IgG anti-dsDNA antibody, total IgG, and cytokine amounts in the culture supernatants and protein kinase C (PKC) activity of T cells were measured by using ELISA. RESULTS: GQ1b enhanced both anti-dsDNA and total IgG production of PBMCs from patients with SLE who were seropositive for anti-dsDNA. Among the seropositive patients, the active patients were more responsive to GQ1b in anti-dsDNA production than the inactive patients. GQ1b also enhanced total IgG production of PBMCs from patients with SLE who were seronegative for anti-dsDNA but did not induce their anti-dsDNA production. In contrast to PBMCs, GQ1b did not affect the antibody production either of purified CD5(+) or of CD5(-) B cells. Anti-IL-6 or anti-IL-10 antibody each partially blocked the GQ1b-induced enhancement of antibody production in PBMCs, and the addition of both antibodies completely blocked the enhancement. GQ1b increased IL-6 and IL-10 production of T cells. The supernatant from GQ1b-treated T cells enhanced antibody production both of CD5(+) and of CD5(-) B cells to a greater extent than that from medium-treated T cells. Exogenous IL-6 and IL-10 additively increased the antibody production both of CD5(+) and CD5(-) B cells. GQ1b-induced increases in IL-6 and IL-10 production of T cells were both blocked by PKC inhibitors, calphostin C and staurosporine. GQ1b enhanced PKC activity of T cells. CONCLUSION: These results suggest that GQ1b may polyclonally increase the production of IgG, including IgG anti-dsDNA antibody, in PBMCs from patients with SLE by promoting IL-6 and IL-10 production of T cells through the enhancement of their PKC activity.
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