Bryostatin-1 specifically inhibits in vitro IgE synthesis

Bryostatin-1, a macrocyclic lactone, is an antineoplastic agent that potent ly activates protein kinase C. Bryostatin-1 (Bryo) had an immunomodulatory effect on murine B cells in that it specifically inhibited IgE production. IgE levels were inhibited in a B cell dose-response curve, whereas IgM and IgG1 were induced by Bryo treatment. Taken together, ELISPOT and surface Ig staining data suggested that Bryo inhibition occurred at the level of clas s switching. RT-PCR and real time PCR data showed that this inhibition was achieved at an early step in switch recombination, namely, the appearance o f Ie germline transcripts. Although Bryo caused a delay in the proliferativ e response of IL-4/CD40 ligand trimer-stimulated B cells, CFSE studies reve aled that the Bryo-mediated inhibition of class switching to IgE occurred i ndependently of the number of division cycles. Notably, Bryo showed the sam e specific IgE inhibition in human B cells. This study provides evidence fo r a unique mechanism regulating IgE production possibly downstream of PKC b y specifically modulating I epsilon germline transcription.