Releasability of human basophils: cellular sensitivity and maximal histamine release are independent variables

Within the atopic and nonatopic population, basophils display a wide variation in the extent of histamine release when challenged with an optimal concentration of polyclonal anti-IgE antibody. We have tested the hypothesis that the maximum percent histamine release obtainable with this stimulus is an indicator of basophil sensitivity. We have defined basophil sensitivity, in the context of IgE-mediated release, as the number of cell-surface IgE molecules required to obtain a half-maximal IgE-mediated response, and we have examined this parameter in the basophils of 39 donors. Sensitizing basophils with various densities of antigen-specific IgE, and measuring histamine release at these measured densities, allowed a determination of basophil sensitivity in 38 of the donors. Basophil sensitivities ranged from 300 to 40,000 molecules per basophil (point of 50% maximal response), although most donors fell in the 800 to 8000 range, with 1900 molecules per basophil as the median response. The maximal response, after challenge with an optimal concentration of either polyclonal or monoclonal anti-IgE antibody, ranged from 8% to 94% (median, 50%). There was no correlation between basophil sensitivity and the maximum histamine release obtained by a challenge with anti-IgE antibody. Therefore two independent variables appeared to control the IgE-mediated response in basophils, similar to the parameters of efficacy and potency in drug studies. In the IgE-mediated response one parameter is the maximum histamine release obtainable through IgE-mediated mechanisms, and the second parameter is basophil sensitivity as defined above. As a byproduct of these studies, we also found that the density of unoccupied high-affinity receptors for IgE antibody was uncorrelated with the total receptor density (range, 4200 to 572,000 receptors per basophil). Indeed, the density of unoccupied receptors was remarkably constant across this large range of total receptor densities.