INDUCTION OF HUMAN IGE SYNTHESIS IN B-CELLS BY MAST-CELLS AND BASOPHILS

IMMUNOGLOBULIN E (IgE) is central to the induction of allergic disease s through its binding to the high-affinity receptor (FcepsilonR1) on m ast cells and basophils. Crosslinking by allergens of the bound IgE le ads to the release of various inflammatory mediators. IgE production b y B cells requires a physical interaction with T cells1, involving a n umber of surface adhesion molecules1,2, as well as the soluble factors interleukin-4 (IL-4)3,4 and IL-13 (ref. 5) produced by T cells6,7, ba sophils8 and mast cells9. Here we report that, in the presence of IL-4 , mast and basophilic cell lines can provide the cell contact signals that are required for IgE synthesis. The human cell lines HMC-1 (mast) and KU812 (basophilic) both express the ligand for CD40 (CD40L) which is shown to be responsible for the IgE production. Moreover, freshly isolated purified human lung mast cells and blood basophils are also s hown to express CD40L and to induce IgE production. This evidence sugg ests that mast cells and basophils may therefore play a key role in al lergy not only by producing inflammatory mediators, but also by direct ly regulating IgE production independently of T cells.