Impaired B Cell Development and Function in the Absence of IκBNS

I kappa BNS has been identified as a member of the I kappa B family of NF-kappa B inhibitors, which undergoes induction upon TCR signaling. Mice carrying a targeted gene disruption of I kappa BNS demonstrate dysregulation of cytokines in T cells, macrophages, and dendritic cells. I kappa BNS mediates both positive and negative gene regulation, depending on individual cell type and/or cytokine. In this study, we demonstrate an additional role for I kappa BNS in the B cell lineage. B cells from I kappa BNS knockout ( KO) mice were impaired in proliferative responses to LPS and anti-CD40. IgM and IgG3 Igs were drastically reduced in the serum of I kappa BNS KO mice, although I kappa BNS KO B cells exhibited a higher level of surface IgM than that found in wild-type mice. Switching to IgG3 was significantly reduced in I kappa BNS KO B cells. The in vitro induction of plasma cell development demonstrated that progression to Ab-secreting cells was impaired in I kappa BNS KO B cells. In agreement with this finding, the number of Ab-secreting cells in the spleens of I kappa BNS KO mice was reduced and production of Ag-specific Igs was lower in I kappa BNS KO mice after influenza infection as compared with wild-type mice. Additionally, I kappa BNS KO mice lacked B1 B cells and exhibited a reduction in marginal zone B cells. Thus, I kappa BNS significantly impacts the development and functions of B cells and plasma cells. The Journal of Immunology, 2011, 187: 3942-3952.