Retinoids as Ig isotype-switch modulators. The role of retinoids in directing isotype switching to IgA and IgG1 (IgE) in association with IL-4 and IL-5.
The role of retinoids was analyzed in directing isotype switching to IgA and IgG1 (IgE) by LPS-stimulated murine mu(+)B-cells in the presence of two Th2-type cytokines, IL-4 and IL-5. All trans retinoic acid (RA) enhanced the production of IgA at high concentrations (10-100 nM) in the presence of IL-5. Addition of IL-4 to the system modulated the IgA response in a dose-dependent manner. Namely, IL-4 inhibited the response at concentrations higher than 250 u/ml, but showed slight enhancement at lower concentrations (130 u/ml). IL-4 alone, which is considered to be an IgE isotype-switch inducer, strongly enhanced the IgG1 and IgE responses. Addition of IL-5 to the system showed a synergistic effect which could be attenuated by addition of low concentrations of RA (about 1 nM). Thus, the presence of switch modulators such as IL-4 and IL-5, their concentration ratios, and concentrations of retinoids are crucial factors in initiating and directing isotype switching to IgA and IgG1 (IgE).
Tokuyama
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Y
Department of Nuclear Medicine, Faculty of Medicine, Kanazawa University, Ishikawa-ken, Japan.
Tokuyama
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H
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D007070:Immunoglobulin A / Q000276:immunology; D017578:Immunoglobulin Class Switching / Q000276:immunology*; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D014212:Tretinoin / Q000276:immunology*; D014801:Vitamin A / Q000276:immunology
D007070:Immunoglobulin A; D007074:Immunoglobulin G; D015848:Interleukin-5; D014801:Vitamin A; D015847:Interleukin-4; D007073:Immunoglobulin E; D014212:Tretinoin