Effects of interleukin-4 and interferon-gamma on the secretion of IgG4 from human peripheral blood mononuclear cells

Whereas IgE antibodies are linked with allergy, IgG4 antibodies may reflect the state of immunity and protection against a particular antigen. It has been shown that interleukin (IL)-4 is required for induction of IgE synthesis. In order to elucidate the role of IL-4 in the production of IgG4 and to compare IgG4 and IgE regulatory processes, we quantified these immunoglobulin isotypes after in vitro culture of peripheral blood mononuclear cells (PBMC) in the presence of IL-4. The production of IgG4 was increased by IL-4 under the same conditions which are optimal for IgE production but not among PBMC from all donors, depending on the magnitude of spontaneous IgG4 secretion: IL-4 was effective only when the spontaneous secretion of IgG4 was < 7% of the total IgG secretion; it had no effect when spontaneous IgG4 production was > 7% of total IgG. The IL-4-induced IgE response was consistently obtained when IgG4 was < 7% of total IgG but was markedly diminished or absent when IgG4 was > 7% of total IgG. If Staphylococcus aureus strain Cowan 1 (SAC) was present during the 48-h preincubation step, spontaneous IgG4 production was increased, but the stimulatory effect of this mitogen on immunoglobulin production, including IgG4, was markedly blocked by the addition of IL-4. In contrast, IL-4-induced IgE synthesis was strongly blocked by the presence of SAC. Finally, secretion of IgG4 (spontaneous and IL-4-induced) was suppressed among cells from most donors by interferon-gamma (IFN-gamma).(ABSTRACT TRUNCATED AT 250 WORDS)