Nuclear export of the NF-?B inhibitor I?B? is required for proper B cell and secondary lymphoid tissue formation.

ABSTRACT: The N-terminal nuclear export sequence (NES) of inhibitor of nuclear factor kappa B (NF-?B) alpha (I?B?) promotes NF-?B export from the cell nucleus to the cytoplasm, but the physiological role of this export regulation remains unknown. Here we report the derivation and analysis of genetically targeted mice harboring a germline mutation in I?B? NES. Mature B cells in the mutant mice displayed nuclear accumulation of inactive I?B? complexes containing a NF-?B family member, cRel, causing their spatial separation from the cytoplasmic I?B kinase. This resulted in severe reductions in constitutive and canonical NF-?B activities, synthesis of p100 and RelB NF-?B members, noncanonical NF-?B activity, NF-?B target gene induction, and proliferation and survival responses in B cells. Consequently, mice displayed defective B cell maturation, antibody production, and formation of secondary lymphoid organs and tissues. Thus, I?B? nuclear export is essential to maintain constitutive, canonical, and noncanonical NF-?B activation potentials in mature B cells in vivo.

SUBMITTER: Wuerzberger-Davis SM 

PROVIDER: S-EPMC3111750 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature