DIFFERENTIAL REGULATION OF IgGI AND IgE SYNTHESIS BY INTERLEUKIN

Interleukin 4 (IL-4)/B cell stimulatory factor 1 is a T cell-derived lymphokine that has effects on virtually all cells of hematopoietic origin. In particular, it strikingly enhances the secretion of IgGI and IgE in vitro and of IgE in vivo (1-10). IL-4 acts on cells that lack surface IgG to cause IgG1 production (1, 11), strongly suggesting that it promotes Ig class switching rather than the selective expansion of previously switched cells. In the course of studies using rIL-4 concentrations substantially higher than those previously reported, we observed a number of new and interesting properties of IL-4 in the promotion of IgGI and IgE production by murine B cells stimulated by bacterial LPS in vitro. We report here that the IL-4 dose/IgGI response curve is bimodal with peaks at 100 and 10,000 U IL-4/ml and with a nadir at 600 U/ml. Furthermore, very substantial amounts of IgE (^-1 ug from 2 x 10 4 cells initially cultured) are produced by B cells stimulated with LPS and 10,000 U/ml of IL-4. Finally, marked suppression of IgM and IgG2a as well as IgG3 and IgG2b (12) occurs with IL-4 concentrations of ^-600 U/ml. These stimulatory and suppressive activities cannot be accounted for by changes in viable cell yields or [sH]thymidine incorporation and can be completely reversed by a monoclonal anti-IL-4 antibody. We further demonstrate that IL-4 acts both early and late in the culture period with markedly different effects on IgGI and IgE secretion. Our results indicate that IL-4 differentially regulates IgGI and IgE secretion. Opinions and assertions contained herein are the private ones of the authors and are not to be construed as official or reflecting the views of the Department of Defense or the Uniformed Services University of the Health Sciences. The experiments reported herein were conducted according to the principles set