A Regulatory B Cell Subset with a Unique CD1dhiCD5+ Phenotype Controls T Cell-Dependent Inflammatory Responses

SummaryB cells mediate multiple functions that influence immune and inflammatory responses. In this study, T cell-mediated inflammation was exaggerated in CD19-deficient (Cd19−/−) mice and wild-type mice depleted of CD20+ B cells, whereas inflammation was substantially reduced in mice with hyperactive B cells as a result of CD19 overexpression (hCD19Tg). These inflammatory responses were negatively regulated by a unique CD1dhiCD5+ B cell subset that was absent in Cd19−/− mice, represented only 1%–2% of spleen B220+ cells in wild-type mice, but was expanded to ∼10% of spleen B220+ cells in hCD19Tg mice. Adoptive transfer of these CD1dhiCD5+ B cells normalized inflammation in wild-type mice depleted of CD20+ B cells and in Cd19−/− mice. Remarkably, IL-10 production was restricted to this CD1dhiCD5+ B cell subset, with IL-10 production diminished in Cd19−/− mice, yet increased in hCD19Tg mice. Thereby, CD1dhiCD5+ B cells represent a unique subset of potent regulatory B cells.