The role of CD1d-mediated lipid presentation by regulatory B cells in invariant natural killer T cell suppression of autoimmunity

Regulatory B cells (Bregs) express high levels of CD1d that presents lipid antigens to invariant natural killer T (iNKT) cells. The role of CD1d in Breg biology and the specific contribution to iNKT cell function and in suppressing inflammation remains unknown. Combining chimeric mice, cell depletion and adoptive transfer strategies, we show that CD1d lipid presentation by B cells to iNKT cells is critical for the induction of iNKT cells that down-regulate Th1 and Th17 adaptive immune responses and arthritis, whilst dispensable for Breg development. Mice lacking CD1d-expressing B cells developed exacerbated arthritis compared to wild-type mice and failed to respond to α-GalCer treatment. Absence of lipid presentation by B cells led to altered activation of iNKT cells, with disruption of regulatory pathways including those involved in metabolism and cytokine responses. Thus, we have identified a novel mechanism by which Bregs via CD1d, in an IL-10 independent manner, control and restrain excessive inflammation.