Regulation of the immune response is necessary in order to prevent excessive inflammation and maintain tolerance to self-antigens in the periphery. Despite over 40 years of recognition that B cells with suppressive capacities exist, very little is known about these enigmatic regulatory cells.
Pre-clinical animal studies have proven that regulatory B cells are needed to prevent the development of severe autoimmunity and may even facilitate tumour escape from immunological destruction. We have discovered that exposure to solar ultraviolet (UV) radiation activates a unique subset of autoimmune-protecting regulatory B cells in C57BL/6 mice. These experiments led us to hypothesise that depleting B cells with a monoclonal antibody would be beneficial in the treatment of UV-induced keratinocyte cancers. To test this hypothesis, mice were exposed to a cancer-causing regimen of solar-simulated UV radiation. Once all mice had developed suspected skin tumours (30 weeks post commencement of UV) mice were treated with a mouse-anti-mouse CD20 B cell depleting antibody. Mice depleted of B cells were significantly protected from developing new skin tumours. Indeed, in the absence of B cells, existing skin tumours grew more slowly and overall survival was improved. Thus, B cells are not only a promising target for enhancing the autoimmune-protective effects of sunlight but also for the treatment of aggressive UV-induced keratinocyte cancers.
The advent of B cell-targeting immunotherapies has confirmed that regulatory B cells are also important for our health and may contribute to disease in humans. Future studies therefore aim to harness the power of regulatory B cells by uncovering how they are activated and their mechanism of action.