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Nat Immunol. 2002 Oct;3(10):958-65. Epub 2002 Sep 23.

BAFF-induced NEMO-independent processing of NF-kappa B2 in maturing B cells.

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Laboratory of Immunoregulation, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1876, USA.


NF-kappa B is usually activated by signal-induced, ubiquitin-mediated degradation of its inhibitor, I kappa B. This process is initiated by phosphorylation of I kappa B by the I kappa B kinase (IKK) complex, predominantly by the IKK beta catalytic subunit, and requires the regulatory subunit IKK gamma (NEMO). Another activation pathway, with no known physiological inducers, involves ubiquitin-mediated processing of the NF-kappa B2 inhibitory protein p100 and is dependent on phosphorylation of p100 by IKK alpha. We show here that B cell-activating factor (BAFF) activates this second pathway and that this requires the BAFF receptor (BAFF-R), the NF-kappa B-inducing kinase (NIK) and protein synthesis, but not NEMO. This NEMO-independent cascade is physiologically relevant for the survival and, hence, progression of maturing splenic B cells.

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