Induced regulatory B cells stably expressing IL-10 cure CNS autoimmunity by targeting microglia

B cells can control autoimmunity through interleukin(IL)-10 production. However, there is no protocol to efficiently generate IL-10-producing B cells, which limits the understanding of their differentiation and their development for cell therapy. To overcome this limitation, we performed a high throughput screen and identified a novel small molecule enabling the induction of quasi pure and stable IL-10-producing B cells. These B cells prevented the development of experimental autoimmune encephalomyelitis and cured recipient mice from disease within a few days upon administration at the peak of clinical signs. Their therapeutic effect involved IL-10 provision to microglia and was independent of their cognate interaction with CD4+ T cells. This study reports the generation of induced regulatory B cells (iBregs) for cell therapy against immune-mediated inflammatory diseases. Overall design: B cells were isolated from spleens and cultured for up to 7 days in different conditions: either with N6 compound, CpG or DMSO controls. Cells were harvested, nuceli were prepared and tagmentation was performed. Libraries fro ATAC-seq were generated and sequenced.