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

Nat Immunol. 2002 Oct;3(10):958-65. doi: 10.1038/ni842. Epub 2002 Sep 23.


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.

MeSH terms

  • Animals
  • B-Cell Activating Factor
  • B-Cell Activation Factor Receptor
  • B-Lymphocytes / cytology
  • B-Lymphocytes / metabolism*
  • Cell Differentiation
  • Cell Survival
  • I-kappa B Kinase
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Mice, Knockout
  • NF-kappa B / metabolism*
  • NF-kappa B p50 Subunit
  • NF-kappa B p52 Subunit
  • Protein Processing, Post-Translational*
  • Protein-Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Receptors, Tumor Necrosis Factor / metabolism
  • Time Factors
  • Tumor Necrosis Factor-alpha / metabolism*


  • B-Cell Activating Factor
  • B-Cell Activation Factor Receptor
  • Membrane Proteins
  • NF-kappa B
  • NF-kappa B p50 Subunit
  • NF-kappa B p52 Subunit
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Tumor Necrosis Factor
  • Tnfrsf13c protein, mouse
  • Tnfsf13b protein, mouse
  • Tumor Necrosis Factor-alpha
  • Protein-Serine-Threonine Kinases
  • Chuk protein, mouse
  • I-kappa B Kinase
  • Ikbkb protein, mouse
  • Ikbke protein, mouse
  • NF-kappa B kinase