TRANSFORMING GROWTH-FACTOR-BETA (TGF-BETA) INHIBITION OF EPSTEIN-BARR-VIRUS (EBV)-4 AND INTERLEUKIN-4 (IL-4)-INDUCED IMMUNOGLOBULIN PRODUCTION IN HUMAN B-LYMPHOCYTES

This study reports on the effects of TGFbeta on the secretion of Ig isotypes by highly purified (>99% CD20-positive) human peripheral blood B cells. Stimulation of these B cell preparations with EBV resulted in the secretion of IgM, IgG, and IgA and the addition of IL-4 induced readily detectable levels (>100 ng/ml) of IgE between 10 and 25 days of culture. TGFbeta1 and TGFbeta2 showed similar dose-dependent suppression of IgM, IgG, and IgA, and the relative proportion of IgG and IgA remained unchanged in the presence of TGFbeta. IgE production induced by EBV and IL-4 was significantly inhibited by TGFbeta. TGFbeta effects on Ig secretion were not related to inhibition of B cell proliferation by this cytokine. In contrast to these TGFbeta effects on EBV activation of primary B cells, the constitutive Ig secretion by EBV-transformed B cells was resistant to TGFbeta, while the increase in Ig secretion induced by IL-6 was inhibited by TGFbeta. Thus, TGFbeta inhibits the EBV-induced secretion of the major Ig isotypes in peripheral blood B cells and has differential effects on Ig secretion by transformed B cells.