The Journal of Immunology, Vol 153, Issue 11 4948-4958, Copyright © 1994 by American Association of Immunologists

ARTICLES

Regulation of human IgG subclass production by cytokines. IFN-gamma and IL-6 act antagonistically in the induction of human IgG1 but additively in the induction of IgG2

Y Kawano, T Noma and J Yata
Department of Pediatrics, Saitama Medical School, Japan.

In this study, we investigated the roles of IFN-gamma and IL-6 in the induction of IgG subclasses from PBMC stimulated with PWM. The presence of IFN-gamma in the first half of the culture period dramatically suppressed the production of IgG1, whereas spontaneous IgG2 secretion was sharply enhanced by IFN-gamma when the latter was present throughout the culture period. Endogenous IFN-gamma was shown to be effective in IgG1 and IgG2 production because IgG1 production was enhanced and IgG2 production was inhibited by the addition of anti-IFN- gamma Ab. Because IFN-gamma did not act on the PBMC depleted of surface IgG2-bearing cells to enhance IgG2, IFN-gamma is unlikely to act as a switching factor. Differing from IFN-gamma, IL-6 enhanced every IgG subclass production as a nonswitching factor, although each of IgG subclasses required IL-6 differentially; maximal IgG1 responses and IgG4 responses occurred when IL-6 was present for the entire culture period or the last half of the culture period, whereas maximal IgG3 responses required the presence of IL-6 for the entire culture period and maximal IgG2 responses were seen when IL-6 was present solely during the last half of the culture period. IFN-gamma antagonized the synthesis of IgG1 by IL-6 and cooperated with IL-6 to produce IgG2. This observation was further supported by the fact that the IL-6- induced IgG1 and IgG2 enhancement were respectively up-regulated and down-regulated by anti-IFN-gamma. Altogether, the critical roles of IFN- gamma and IL-6 were implicated.

This article has been cited by other articles:

				A. Dey, P. Sharma, N. S. Redhu, and S. Singh Kinesin Motor Domain of Leishmania donovani as a Future Vaccine Candidate Clin. Vaccine Immunol., May 1, 2008; 15(5): 836 - 842. [Abstract] [Full Text] [PDF]

				T. Peters, W. Bloch, C. Wickenhauser, S. Tawadros, T. Oreshkova, D. Kess, T. Krieg, W. Muller, and K. Scharffetter-Kochanek Terminal B cell differentiation is skewed by deregulated interleukin-6 secretion in {beta}2 integrin-deficient mice J. Leukoc. Biol., September 1, 2006; 80(3): 599 - 607. [Abstract] [Full Text] [PDF]

				T. Kikuchi, D.L. Willis, M. Liu, D.B. Purkall, S. Sukumar, S.E. Barbour, H.A. Schenkein, and J.G. Tew Dendritic-NK Cell Interactions in P. gingivalis-specific Responses J. Dent. Res., September 1, 2005; 84(9): 858 - 862. [Abstract] [Full Text] [PDF]

				T. Kikuchi, D.L. Willis, M. Liu, D.B. Purkall, S. Sukumar, S.E. Barbour, H.A. Schenkein, and J.G. Tew Dendritic-NK Cell Interactions in P. gingivalis-specific Responses Journal of Dental Research, September 1, 2005; 84(9): 858 - 862. [Abstract] [Full Text] [PDF]

				T. Kikuchi, C. L. Hahn, S. Tanaka, S. E. Barbour, H. A. Schenkein, and J. G. Tew Dendritic Cells Stimulated with Actinobacillus actinomycetemcomitans Elicit Rapid Gamma Interferon Responses by Natural Killer Cells Infect. Immun., September 1, 2004; 72(9): 5089 - 5096. [Abstract] [Full Text] [PDF]

				S. Al-Darmaki, K. Knightshead, Y. Ishihara, A. Best, H. A. Schenkein, J. G. Tew, and S. E. Barbour Delineation of the Role of Platelet-Activating Factor in the Immunoglobulin G2 Antibody Response Clin. Vaccine Immunol., July 1, 2004; 11(4): 720 - 728. [Abstract] [Full Text]

				M. Gilliet, M. Kleinhans, E. Lantelme, D. Schadendorf, G. Burg, and F. O. Nestle Intranodal injection of semimature monocyte-derived dendritic cells induces T helper type 1 responses to protein neoantigen Blood, July 1, 2003; 102(1): 36 - 42. [Abstract] [Full Text] [PDF]

				S. E. Barbour, Y. Ishihara, M. Fakher, S. Al-Darmaki, T. H. Caven, C. P. Shelburne, A. M. Best, H. A. Schenkein, and J. G. Tew Monocyte Differentiation in Localized Juvenile Periodontitis Is Skewed toward the Dendritic Cell Phenotype Infect. Immun., June 1, 2002; 70(6): 2780 - 2786. [Abstract] [Full Text] [PDF]

				P. L. W. Yun, A. A. Decarlo, C. Collyer, and N. Hunter Hydrolysis of Interleukin-12 by Porphyromonas gingivalis Major Cysteine Proteinases May Affect Local Gamma Interferon Accumulation and the Th1 or Th2 T-Cell Phenotype in Periodontitis Infect. Immun., September 1, 2001; 69(9): 5650 - 5660. [Abstract] [Full Text] [PDF]

				D. Markine-Goriaynoff, T. D. Nguyen, G. Bigaignon, J. Van Snick, and J.-P. Coutelier Distinct requirements for IL-6 in polyclonal and specific Ig production induced by microorganisms Int. Immunol., September 1, 2001; 13(9): 1185 - 1192. [Abstract] [Full Text] [PDF]

				M. C. Remington, E. L. Munson, S. M. Callister, M. L. Molitor, J. A. Christopherson, D. J. DeCoster, S. D. Lovrich, and R. F. Schell Interleukin-6 Enhances Production of Anti-OspC Immunoglobulin G2b Borreliacidal Antibody Infect. Immun., July 1, 2001; 69(7): 4268 - 4275. [Abstract] [Full Text] [PDF]

				K. Tani, W. J. Murphy, O. Chertov, R. Salcedo, C. Y. Koh, I. Utsunomiya, S. Funakoshi, O. Asai, S. H. Herrmann, J. M. Wang, et al. Defensins act as potent adjuvants that promote cellular and humoral immune responses in mice to a lymphoma idiotype and carrier antigens Int. Immunol., May 1, 2000; 12(5): 691 - 700. [Abstract] [Full Text] [PDF]

				I. Levan-Petit, E. Lelievre, A. Barra, A. Limosin, B. Gombert, J.-L. Preud'homme, and J.-C. Lecron Th2 cytokine dependence of IgD production by normal human B cells Int. Immunol., November 1, 1999; 11(11): 1819 - 1828. [Abstract] [Full Text] [PDF]

				A. J. Pollard, R. Galassini, E. M. Rouppe van der Voort, M. Hibberd, R. Booy, P. Langford, S. Nadel, C. Ison, J. S. Kroll, J. Poolman, et al. Cellular Immune Responses to Neisseria meningitidis in Children Infect. Immun., May 1, 1999; 67(5): 2452 - 2463. [Abstract] [Full Text] [PDF]