We report the molecular characterization of five human monoclonal antibodies, BAB1–5 (BAB1: IgG1; BAB4: IgG2; BAB2, 3, 5: IgG4), 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.
