Nature Immunology
3, 958 - 965 (2002)
Published online: 23 September 2002; | doi:10.1038/ni842
BAFF-induced NEMO-independent processing of NF- B2 in maturing B cellsEstefania Claudio, Keith Brown, Sun Park, Hongshan Wang
& Ulrich Siebenlist
Laboratory of Immunoregulation, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1876, USA.
Correspondence should be addressed to Ulrich Siebenlist us3n@nih.govNF- B is usually activated by signal-induced, ubiquitin-mediated degradation of its inhibitor, IB. This process is initiated by phosphorylation of IB by the IB kinase (IKK) complex, predominantly by the IKK catalytic subunit, and requires the regulatory subunit IKK (NEMO). Another activation pathway, with no known physiological inducers, involves ubiquitin-mediated processing of the NF-B2 inhibitory protein p100 and is dependent on phosphorylation of p100 by IKK . We show here that B cell−activating factor (BAFF) activates this second pathway and that this requires the BAFF receptor (BAFF-R), the NF-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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