MARCH1 down-regulation in IL-10-activated B cells increases MHC class II expression

IL-10 is vastly studied for its anti-inflammatory properties on most immune cells. However, it has been reported that IL-10 activates B cells, up-regulates their MHC class II molecules and prevents apoptosis. As MARCH1 was shown to be responsible for the intracellular sequestration of MHC class II molecules in dendritic cells and monocytes in response to IL-10, we set out to clarify the role of this ubiquitin ligase in B cells. Here, we demonstrate in mice that splenic follicular B cells represent the major cell population that up-regulate MHC II molecules in the presence of IL-10. Activation of these cells through TLR4, CD40 or the IL-10 receptor caused the down-regulation of MARCH1 mRNA. Accordingly, B cells from MARCH1-deficient mice do not up-regulate I-Ab in response to IL-10. In all, our results demonstrate that IL-10 can have opposite effects on MARCH1 regulation in different cell types.

► MARCH1 is down-regulated upon B cell activation.
► MARCH1 is expressed in follicular B cells.
► Follicular B cells up-regulate MHC II in response to IL-10.
► IL-10 down-regulates MARCH1 expression in follicular B cells.
► Regulation of MHC II surface expression by IL-10 is post-translational.