Regulatory B cells mediate tolerance to apoptotic self in health: implications for disease

B cells are able to regulate immune responses through the secretion of IL-10 and other inhibitory cytokines, though no transcription factor that can define 'regulatory B cells' as a separate lineage has yet been found. Instead it is likely that this function arises as a result of the immune context in which B cells find themselves and the stimuli they perceive. However, some B cells found within the B1a and the marginal zone subsets have a greater propensity to produce IL-10 than others. What are the natural stimuli for these cells to induce immune regulation? We discuss the role that the recognition of autoantigens exposed by apoptotic cells plays in stimulating IL-10 production in mouse and human studies. This mechanism involves the recognition and uptake of self-antigens by autoreactive BCRs, for delivery to endocytic compartments, where apoptosis-derived DNA binds to TLR9, driving IL-10 production. These 'natural' regulatory B cells represent a way of maintaining tolerance to self. We discuss how this may operate in inflammatory lesions where there is an excess of apoptotic leukocytes and how this impacts on our understanding of autoimmune disease.