The compositions and methods described herein are based, in part, on the discovery that regulatory B cells (Bregs) differentially express a specific set of coinhibitory molecules, including TIGIT, LAG-3, PD-1, CTLA4, and TIM-3. The data described herein indicate that TIGIT is required for both Breg-mediated tolerance maintenance at the steady state, and inflammation restraint during autoimmune and inflammatory diseases. Accordingly, provided herein are compositions and methods targeting coinhibitory molecules, such as TIGIT, LAG-3, PD-1, CTLA4, and TIM-3, in B cells, as novel therapeutic strategies for modulating immune suppression and treating diseases mediated or impacted by immune suppression mechanisms, such as autoimmune diseases and cancers.
