Soluble CD23 does not cross-link IgE bound to FcϵRI on mast cells. The ability of soluble CD23 to engage IgE on B cells and mast cells was tested. A, after preincubation of IgE, the addition of anti-IgE antibody resulted in activation of the FcϵRIα+ LAD-2 mast cell line, as measured by release of β-hexosaminidase. Neither monomeric derCD23 nor trimeric triCD23 was able to cross-link IgE and activate mast cells in this assay. B, in contrast, triCD23 effectively cross-links membrane IgE on the surface of IgE+ human tonsillar B cells, resulting in activation of these cells and increased secretion of IgE. B cell cultures were activated with IL-4 and anti-CD40, and soluble CD23 was added at 1 μm; supernatants were harvested 12 days after activation, tested for IgE levels, and compared with levels for cells treated with IL-4/anti-CD40 alone (* = p < 0.05; ** = p < 0.01). The regulatory activities of soluble CD23 on IgE+ B cells are described in detail in Ref. 19.