Ganglioside GQ1b enhances anti-double-stranded DNA antibody and IgG production of PBMCs from patients with systemic lupus erythematosus.
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.
Kanda
N
N
Department of Dermatology, Teikyo University, School of Medicine, Tokyo, Japan.
Watanabe
S
S
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
D000276:Adjuvants, Immunologic; D000906:Antibodies; D018956:CD5 Antigens; D016207:Cytokines; D005732:Gangliosides; D007074:Immunoglobulin G; C039129:GQ1b ganglioside; D004247:DNA