Molecular characterization of human IgG monoclonal antibodies specific for the major birch pollen allergen Bet v 1.: Anti-allergen IgG can enhance the anaphylactic reaction

We report the molecular characterization of five human monoclonal antibodies, BAB1-5 (BAB1 : IgG(1) ; BAB4: IgG(2); BAE2, 3, 5: IgG(4)), with specificity for the major birch pollen allergen, Bet v 1. BAB1-5 were obtained after immunotherapy and contained a high degree of somatic mutations indicative of an antigen-driven affinity maturation process. While BAB1 inhibited the binding of patients IgE to Bet v 1, BAB2 increased IgE recognition of Bet v 1, and, even as Escherichia coli-expressed Fab, augmented Bet v 1-induced immediate type skin reactions. The demonstration that IgG antibodies can enhance allergen-induced allergic reactions is likely to explain the unpredictability of specific immunotherapy. (C) 2000 Federation of European Biochemical Societies.