Class-switch recombination (CSR) in mature B cells activated under T helper 2 (TH2)-type conditions generates IgG1 and IgE isotypes. Now, Wesemann et al. report that CSR during early B cell developmental stages favours the IgE over the IgG1 isotype. Activated immature B cells derived from fetal liver progenitors, as well as activated CD93+ transitional B cells, showed an increased preference for switching to the IgE isotype compared with activated mature B cells. Whereas activated mature B cells have been previously shown to switch to IgE in a two-step process, through an intermediate IgG1 stage, activated immature B cells were observed to undergo direct IgM to IgE transition. The underlying mechanism may involve decreased levels of phosphorylated signal transducer and activator of transcription 6 (STAT6) and altered histone methylation at the germline promoter region upstream of the constant IgG1 heavy chain gene. These findings can explain the elevated serum IgE levels in children and in immunodeficient patients with defective B cell development.