It remains to be elucidated which leukocyte populations are required for CpG induction of neuroprotection. Bregs offer potential as they are known to be immunosuppressive, and CpG has been reported to drive the differentiation of B cells into Bregs [34]. In line with a protective role for Bregs prior to stroke, Bodhankar et al. [26] showed that adoptive transfer of Bregs 24 h before cerebral ischemia reduces infarct size. Mice receiving IL-10-secreting B cells showed an increase of regulatory cell populations in the periphery and reduced infiltration of T cells and proinflammatory cytokines levels in the ischemic hemisphere. These results show that the increased presence of Bregs before stroke can modulate the inflammatory response, potentially contributing to protection against subsequent ischemia. In further support, Monson et al. [7] found that repetitive hypoxic preconditioning (RHP) induces an immunosuppressive phenotype in resident B cells before stroke and results in decreased infiltration of leukocytes in the brain following stroke. It appeared that RHP reprograms B cells to downregulate genes involved in T cell differentiation and B-T cell interactions [7].