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IB Kinase Signaling Is Essential for Maintenance of Mature B Cells

Manolis Pasparakis^1,3, Marc Schmidt-Supprian^1,2 and Klaus Rajewsky^1,2

¹ Institute for Genetics, University of Cologne, D-50931 Cologne, Germany
² Center for Blood Research, Harvard Medical School, Boston, MA 02115
³ EMBL Mouse Biology Programme, I-00016 Monterotondo, Italy

Address correspondence to Klaus Rajewsky, Center for Blood Research Harvard Medical School, 200 Longwood Ave., Boston, MA 02115. Phone: 617-278-3132; Fax: 617-278-3129; E-mail: rajewsky{at}cbr.med.harvard.edu

Nuclear factor (NF)-B proteins play crucial roles in immune responses and cellular survival. Activation of NF-B is mediated by the IB kinase (IKK) complex, which is composed of two kinases, IKK1 and IKK2, and a regulatory subunit termed NF-B 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-B.

Key Words: NF-B • IKK • CD19-Cre • B cell subsets • maintenance

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