The activation of B cells by pathogens to elicit antibody production is a central facet of immunity. Pathogens also evoke the expansion of B cells that can function in the regulation of immunity. Different pathogens have been described with the capacity to drive such regulatory B (Breg) cells. One group of pathogens, parasitic helminths, has been used experimentally to identify and explore immunological mechanisms of Breg cells. Several species of helminths have demonstrated the capacity to expand Breg cell populations in mice, while the presence of Breg cells in humans infected with certain helminths has also been identified. Herein, we outline how the helminth Schistosoma mansoni can expand Breg cellular responses in vitro. We describe the establishment of a laboratory-based S. mansoni life cycle and methodology for detecting Breg cells via flow cytometry.