Control of Allergen-Induced Histamine Secretion by Human Basophils with F(ab) of Anti-IgE Antibodies

A strategy was developed to obtain univalent F(ab) fragments against IgE, which would interfere with IgE-mediated activation of target cells, but lacked their activity due to cross-linking of IgE bound to Fc(epsilon)-receptors. Two kinds of mouse anti-human IgE monoclonal antibodies (mAb) against CH(2) or CH(3) domains induced histamine release from basophils of allergic patients and healthy donors. F(ab')(2) fragments of the mAb (0.01 - 10.0 &mgr;g/ml) possessed the same activity. On the contrary, F(ab) fragments of the mAb did not activate basophils, but in concentrations up to 10.0 &mgr;g/ml they inhibited, both in direct and cross reaction, histamine secretion induced by anti-IgE mAb and their F(ab')(2) fragments. Allergen-induced histamine release from basophils of pollen-sensitive patients was also inhibited by F(ab) fragments of anti-IgE mAb. It was suggested that univalent F(ab) fragments of anti-IgE mAb binding to cell-fixed IgE molecules modified their allergen-induced conformation and, as a result of that, inhibited mediator release from the cells.