What are regulatory B cells?

B cells are now acknowledged to play multiple roles in the immune response, in addition to making antibodies. Their role in regulating T-cell responses during inflammation has come into focus recently. Thus, IL-10 production by B cells has been shown to be important in limiting auto-reactive and pathogen-driven immune pathology; however, the exact identity of the regulatory B cells remains elusive; do they belong to a committed subset or can all B cells regulate given the appropriate inducing stimuli? A study in this issue of the European Journal of Immunology provides insight into the IL-10-producing B cells in humans, suggesting that many B cells have the capacity to make IL-10 when optimally stimulated via the BCR and TLR9. Despite producing significant amounts of inflammatory cytokines as well, these B cells suppress T-cell proliferation. This Commentary places this study in the context of what we think we know about regulatory B cells and more importantly highlights the questions we still need to answer.