INHIBITION OF HUMAN IGE SYNTHESIS BY ANTI-IGE ANTIBODIES REQUIRES DIVALENT RECOGNITION

We used a selection of well-characterized murine monoclonal anti-IgE a ntibodies to investigate their effect on human in vitro IgE synthesis. We found anti-IgE antibodies that either inhibited or enhanced interl eukin-4 plus anti-CD40-induced in vitro IgE synthesis in peripheral bl ood mononuclear cells (PBMC). This differential activity was isotype s pecific as neither IgM nor IgG synthesis were affected. Interestingly, only coding IgE mRNA was down-regulated, whereas germ-line epsilon RN A expression was not influenced by anti-IgE monoclonal antibody (mAb). On purified B cells all anti-IgE mAb inhibited interleukin-4 plus ant i-CD40-induced IgE synthesis, implying a role of non-B cells for the e nhancing activity observed in PBMC. Using Fab and F(ab')(2) of an inhi bitory anti-IgE mAb we could show that divalent recognition was requir ed for inhibition of IgE synthesis.