Retinoids as Ig Isotype-Switch Modulators

The role of retinoids was analyzed in directing isotype switching to IgA and IgG1 (IgE) by LPS-stimulated murine μ(+)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 usolidusml, but showed slight enhancement at lower concentrations (130 usolidusml). 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).