The atypical IκB protein IκB_NS is important for Toll‐like receptor‐induced interleukin‐10 production in B cells

Abstract

SummaryAlthough 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 IjB NS , an inducible nuclear IjB protein, is important for Toll-like receptor (TLR)-mediated IL-10 production in B cells. Studies using IjB NS knockout mice revealed that the number of IL-10-producing B cells is reduced in IjB NS À/À spleens and that the TLR-

Multiple Functions of B Cells in the Pathogenesis of Systemic Lupus Erythematosus

“…Adoptive transfer of LPS-activated B cells significantly ameliorated the disease procession in non-obese diabetic (NOD) mice [138]. In addition, TLR2 ligands, such as Pam3CSK4 and FSL1, and TLR7 ligand, such as imiquimod, also induced the secretion of IL-10 in B cells and triggered the generation of Bregs [140].…”

“…Depletion of Myd88 in B cells limited IL-10 secreting capacities of B cells both in vitro and in vivo. Moreover, one atypical IκB protein (IκBNS) also played important roles in TLR-ligation-induced Breg generation [140]. Mice deficient for IκBNS showed reduced frequencies of CD1d + CD5 + Bregs, along with the limited responsiveness of IL-10-secreting Breg generation upon TLR2-, TLR4-, TLR7-, or TLR9-ligation [140].…”

A Hypermorphic Nfkbid Allele Contributes to Impaired Thymic Deletion of Autoreactive Diabetogenic CD8+ T Cells in NOD Mice

“…In the B-cell compartment, Nfkbid expression is necessary for development of the MZ and B1-a subsets as well as the generation of antibody responses to T-dependent and independent antigens (34, 38, 42–44). Nfkbid deficiency was also associated with an impairment in IL-10 secreting B-lymphocytes (45). Nfkbid deficient T-cells have impaired in vitro proliferation and cytokine secretion (IL-2, IFN-γ) (34).…”

A hypermorphic Nfkbid allele represents an Idd7 locus gene contributing to impaired thymic deletion of autoreactive diabetogenic CD8+ T-cells in NOD mice

“…In the B-cell compartment, Nfkbid expression is necessary for development of the MZ and B1-a subsets as well as the generation of antibody responses to T-dependent and independent antigens (22, 43, 46–48). Nfkbid deficiency was also associated with an impairment in IL-10 secreting B-lymphocytes (49). Nfkbid deficient T-cells have impaired in vitro proliferation and cytokine secretion (IL-2, IFN-γ) (22).…”