[Regulation of the production of IgE in man]

Allergy is associated with elevated production of allergen-specific IgE antibody. Naive allergen-specific B cells undergo a series of molecular interactions before they would produce allergen-specific IgE antibody. Besides allergen recognition, specific B cells have to receive signals from cell-surface proteins and cytokines from their various cellular partners. Activated T cells express a ligand for CD40 that rescues germinal centre B cells from programmed cell death. Contact with follicular dendritic cells or other T and B cells promotes differentiation into plasma through engagement of two pairs of complementary cell-surface proteins, CD21/CD23. Among the many cytokines secreted by helper T cells, interleukin-4 is necessary for the class switch to IgE, and IL-13 also triggers switching to IgE. Then, IgE would participate to feed-back regulation of its production by acting at different levels. When bound to CD23, also known as Fc epsilon receptor type II, IgE immune complexes inhibit CD21/CD23 cell-cell interactions. When bound to Fc epsilon receptor type I on Langerhans' cells in the skin or mucosa, IgE antibody enhances allergen presentation to T cells and promotes their differentiation into type 2 helper T cells that secrete IL-4 but no interferon-gamma. Local activation of mast cells or basophils, via their Fc epsilon Receptor type I-bound IgE, would trigger secretion of various cytokines, IL-4 in particular, and expression of CD21 and CD40 ligand, which altogether could replace contact with T cells to deliver the co-stimulatory signals for localised IgE production.(ABSTRACT TRUNCATED AT 250 WORDS)