| First Author | Wuerzberger-Davis SM | Year | 2011 |
| Journal | Immunity | Volume | 34 |
| Issue | 2 | Pages | 188-200 |
| PubMed ID | 21333553 | Mgi Jnum | J:168977 |
| Mgi Id | MGI:4939507 | Doi | 10.1016/j.immuni.2011.01.014 |
| Citation | Wuerzberger-Davis SM, et al. (2011) Nuclear Export of the NF-kappaB Inhibitor IkappaBalpha Is Required for Proper B Cell and Secondary Lymphoid Tissue Formation. Immunity 34(2):188-200 |
| abstractText | The N-terminal nuclear export sequence (NES) of inhibitor of nuclear factor kappa B (NF-kappaB) alpha (IkappaBalpha) promotes NF-kappaB 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 IkappaBalpha NES. Mature B cells in the mutant mice displayed nuclear accumulation of inactive IkappaBalpha complexes containing a NF-kappaB family member, cRel, causing their spatial separation from the cytoplasmic IkappaB kinase. This resulted in severe reductions in constitutive and canonical NF-kappaB activities, synthesis of p100 and RelB NF-kappaB members, noncanonical NF-kappaB activity, NF-kappaB 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, IkappaBalpha nuclear export is essential to maintain constitutive, canonical, and noncanonical NF-kappaB activation potentials in mature B cells in vivo. |
