The atypical I κ B protein I κ B NS is important for Toll‐like receptor‐induced interleukin‐10 production in B cells

Summary Although a major function of B cells is to mediate humoral immunity by producing antigen‐specific antibodies, a specific subset of B cells is important for immune suppression, which is mainly mediated by the secretion of the anti‐inflammatory cytokine interleukin‐10 ( IL ‐10). However, the mechanism by which IL ‐10 is induced in B cells has not been fully elucidated. Here, we report that I κ B NS , an inducible nuclear I κ B protein, is important for Toll‐like receptor ( TLR )‐mediated IL ‐10 production in B cells. Studies using I κ B NS knockout mice revealed that the number of IL ‐10‐producing B cells is reduced in I κ B NS −/− spleens and that the TLR ‐mediated induction of cytoplasmic IL ‐10‐positive cells and IL ‐10 secretion in B cells are impaired in the absence of I κ B NS . The impairment of IL ‐10 production by a lack of I κ B NS was not observed in TLR ‐triggered macrophages or T‐cell‐receptor‐stimulated CD 4 + CD 25 + T cells. In addition, I κ B NS ‐deficient B cells showed reduced expression of Prdm1 and Irf4 and failed to generate IL ‐10 + CD 138 + plasmablasts. These results suggest that I κ B NS is selectively required for IL ‐10 production in B cells responding to TLR signals, so defining an additional role for I κ B NS in the control of the B‐cell‐mediated immune responses.