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Infection with the helminth Schistosoma mansoni drives the development of IL-10-producing regulatory B cells (Breg cells) which suppress experimental allergic airway inflammation. Here we investigated whether schistosomal egg antigens (SEA) directly interact with B cells and induce development of IL-10-producing Breg cells. Splenic B cell cytokine production and regulatory capacity was analysed after repeated intraperitoneal injection of SEA into C57BL/6 mice. To identify cell types that bind SEA in vivo, mice were intravenously injected with fluorescently labeled SEA and spleens analysed by immunohistochemistry and flow cytometry. For in vitro assays, naive CD19 sorted splenic B cells were cultured with SEA to study binding as well as B cell cytokines and regulatory capacity. SEA treatment upregulated IL-10, CD40 and CD86 expression by splenic marginal zone (MZ) B cells in vivo, and MZ B cells as well as MZ macrophages bound SEA. Importantly, SEA could also induce Breg cell development in vitro which was further increased by CD40 ligation, whereas TLR2- and TLR4-signaling was not involved. SEA-induced Breg cells triggered regulatory T cell development and suppressed T cell IFN-γ production in co-culture experiments. Macrophages were dispensable for Breg induction as shown by macrophage depletion in SEA-treated mice. In conclusion, schistosomal egg antigens can drive Breg cell development by targeting B cells directly. Current work focuses on the identification of relevant molecules in SEA and the role of pattern-recognition receptors to provide new insights in the generation of Breg cells. This may form a basis for novel therapies against allergic disorders by enhancing Breg cell activity.