title: Ganglioside GQ1b enhances anti-double-stranded DNA antibody and IgG production of PBMCs from patients with systemic lupus erythematosus.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Dermatology, Teikyo University, School of Medicine, Tokyo, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Kanda
authors.forename: S
authors.initials: S
authors.lastname: Watanabe
mesh_terms: D000276:Adjuvants, Immunologic / Q000037:antagonists & inhibitors / Q000502:physiology; D000328:Adult; D000906:Antibodies / Q000494:pharmacology / Q000502:physiology; D015551:Autoimmunity / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D018956:CD5 Antigens / Q000032:analysis; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004247:DNA / Q000276:immunology*; D005260:Female; D005732:Gangliosides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000097:blood*; D008297:Male; D008875:Middle Aged; D015398:Signal Transduction / Q000502:physiology
chemical_list: D000276:Adjuvants, Immunologic; D000906:Antibodies; D018956:CD5 Antigens; D016207:Cytokines; D005732:Gangliosides; D007074:Immunoglobulin G; C039129:GQ1b ganglioside; D004247:DNA