First Author | Touma M | Year | 2011 |
Journal | J Immunol | Volume | 187 |
Issue | 8 | Pages | 3942-52 |
PubMed ID | 21900180 | Mgi Jnum | J:179321 |
Mgi Id | MGI:5301780 | Doi | 10.4049/jimmunol.1002109 |
Citation | Touma M, et al. (2011) Impaired B cell development and function in the absence of IkappaBNS. J Immunol 187(8):3942-52 |
abstractText | IkappaBNS has been identified as a member of the IkappaB family of NF-kappaB inhibitors, which undergoes induction upon TCR signaling. Mice carrying a targeted gene disruption of IkappaBNS demonstrate dysregulation of cytokines in T cells, macrophages, and dendritic cells. IkappaBNS mediates both positive and negative gene regulation, depending on individual cell type and/or cytokine. In this study, we demonstrate an additional role for IkappaBNS in the B cell lineage. B cells from IkappaBNS knockout (KO) mice were impaired in proliferative responses to LPS and anti-CD40. IgM and IgG3 Igs were drastically reduced in the serum of IkappaBNS KO mice, although IkappaBNS KO B cells exhibited a higher level of surface IgM than that found in wild-type mice. Switching to IgG3 was significantly reduced in IkappaBNS KO B cells. The in vitro induction of plasma cell development demonstrated that progression to Ab-secreting cells was impaired in IkappaBNS KO B cells. In agreement with this finding, the number of Ab-secreting cells in the spleens of IkappaBNS KO mice was reduced and production of Ag-specific Igs was lower in IkappaBNS KO mice after influenza infection as compared with wild-type mice. Additionally, IkappaBNS KO mice lacked B1 B cells and exhibited a reduction in marginal zone B cells. Thus, IkappaBNS significantly impacts the development and functions of B cells and plasma cells. |