IkappaB kinase signaling is essential for maintenance of mature B cells.
Nuclear factor (NF)-kappaB proteins play crucial roles in immune responses and cellular survival. Activation of NF-kappaB is mediated by the IkappaB kinase (IKK) complex, which is composed of two kinases, IKK1 and IKK2, and a regulatory subunit termed NF-kappaB essential modulator (NEMO). IKK2- and NEMO-deficient mice die at early embryonic stages. We therefore used conditional gene targeting to evaluate the role of these proteins in B cells in adult mice. B lineage-specific disruption of either IKK signaling by deletion of NEMO, or of IKK2-specific signals by ablation of IKK2 activity leads to the disappearance of mature B lymphocytes. We conclude that maintenance of mature B cells depends on IKK-mediated activation of NF-kappaB.
Pasparakis
Manolis
M
Institute for Genetics, University of Cologne, D-50931 Cologne, Germany.
Schmidt-Supprian
Marc
M
Rajewsky
Klaus
K
D000818:Animals; D018941:Antigens, CD19 / Q000502:physiology; D001402:B-Lymphocytes / Q000502:physiology*; D005434:Flow Cytometry; D051550:I-kappa B Kinase; D019426:Integrases / Q000502:physiology; D051379:Mice; D016328:NF-kappa B / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D014764:Viral Proteins / Q000502:physiology
D018941:Antigens, CD19; D016328:NF-kappa B; D014764:Viral Proteins; D017346:Protein Serine-Threonine Kinases; C496564:Chuk protein, mouse; D051550:I-kappa B Kinase; C496562:Ikbkb protein, mouse; C496566:Ikbke protein, mouse; C045073:Cre recombinase; D019426:Integrases