Differential regulation of IgG1 and IgE synthesis by interleukin 4

Abstract

IL-4/B cell stimulatory factor-1 is a T cell-derived lymphokine that has been shown to enhance IgG1 and IgE and to suppress IgG3 and IgG2b secretion by B cells stimulated with bacterial LPS. We show here that the stimulation of IgG1 and IgE secretion in response to rIL-4 is differentially regulated. The dose-response curve for IgG1 production is bimodal with peaks at 100 and 10,000 U/ml. IgE production is modest at 100 U/ml and exhibits a progressive enhancement as the IL-4 concentration is increased to 10,000 U/ml, reaching approximately 1 microgram of IgE from an initial cell number of 2 X 10(4). Both of these effects are reversed by monoclonal anti-IL-4 antibody. Neither the enhancing nor suppressing effects of IL-4 can be explained by changes in viable cell yields or [3H]thymidine incorporation. The production of both IgG1 and IgE is controlled by IL-4 in a two-phase manner. During the initial 2 d of culture with LPS, IL-4 action for both IgG1 and IgE production is relatively concentration independent at doses greater than 600 U/ml. This 2-d treatment leads to maximal IgG1 production at day 6 with no further addition of IL-4. Addition of IL-4 during the final 4 d of culture has no effect at concentrations under 100 U/ml. At higher concentrations, IL-4 is strikingly suppressive for IgG1 production. By contrast, little IgE is produced unless IL-4 is present after 2 d of culture and the response is directly dependent on the concentration of IL-4 during this second phase of culture with maximal responses observed at 10,000 U/ml. These differences in IL-4 requirements for IgG1 and IgE production, respectively, may have an important role in the regulation of the synthesis of these isotypes in responses to microbial antigens.