Regulation of human IgG subclass production by cytokines: human IgG subclass production enhanced differentially by interleukin-6.
Peripheral blood mononuclear cells (PBMC) stimulated with pokeweed mitogen (PWM) produced increased IgG when cultured with interleukin-6 (IL-6). IgG subclass analysis showed that the presence of IL-6 during the last half of the culture period enhanced IgG1 and IgG4 production. Enhancement of IgG2 synthesis required the presence of IL-6 solely during the last half of the culture period, whereas enhancement paradoxically was blocked by its presence during the first half. The IgG3-enhancing effect of IL-6 was observed only when IL-6 was present throughout the culture period. The critical role of IL-6 was supported by the inhibition of IgG subclass synthesis by anti-IL-6 antibody. PBMC depleted of cells bearing surface IgG of a particular subclass did not synthesize that subclass. This non-responsiveness, which was not reversed even by an addition of IL-6, indicates that the main action of IL-6 is on the differentiation of committed B cells. In addition, IL-6 triggered T cells to produce significant helper activity. These results indicate that IL-6 enhances IgG subclass production differentially and that its critical role in IgG subclass synthesis is in part mediated by T cells, as well as by its direct action on B cells. These findings should be useful for analysing such immune disorders as IgG subclass deficiencies and autoimmune diseases.
Kawano
Y
Y
Department of Pediatrics, Saitama Medical School, Japan.
Noma
T
T
Kou
K
K
Yoshizawa
I
I
Yata
J
J
D000328:Adult; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000187:drug effects; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000145:classification; D015850:Interleukin-6 / Q000276:immunology / Q000494:pharmacology*; D007700:Kinetics; D011043:Pokeweed Mitogens / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*
D000888:Antibodies, Anti-Idiotypic; D007074:Immunoglobulin G; D015850:Interleukin-6; D011043:Pokeweed Mitogens; D011994:Recombinant Proteins