Effects of W iskott– A ldrich Syndrome Protein Deficiency on IL ‐10‐Producing Regulatory B Cells in Humans and Mice

The W iskott– A ldrich syndrome protein ( WAS p) is an important regulator of the actin cytoskeleton and is required for immune cell function. WAS p deficiency causes a marked reduction in major mature peripheral B cell subsets, particularly marginal zone ( MZ ) B cells. We hypothesized that WAS p deficiency may also lead to a reduction of regulatory B cells (known as B 10 cells) belonging to a novel subset of B cells. And in consideration of the key role of B 10 cells play in maintaining peripheral tolerance, we conjectured that a deficit of these cells could contribute to the autoimmunity in patients with W iskott– A ldrich syndrome ( WAS ). The effects of WAS p deficiency on B 10 cells have been reported by only one group, which used an antigen‐induced arthritis model. To add more information, we measured the percentage of B 10 cells, regulatory T cells ( T regs) and T h1 cells in WAS p knockout ( WAS p KO ) mice. We also measured the percentage of B 10 cells in patients with WAS by flow cytometry. Importantly, we used the non‐induced autoimmune WAS p KO mouse model to investigate the association between B 10 cell frequency and the T reg/ T h1 balance. We found that the percentage of B 10 cells was reduced in both mice (steady state and inflammatory state) and in humans and that the lower B 10 population correlated with an imbalance in the T reg/ T h1 ratio in old WAS p KO mice with autoimmune colitis. These findings suggest that WAS p plays a crucial role in B 10 cell development and that WAS p‐deficient B 10 cells may contribute to autoimmunity in WAS .