BAFF/BLyS receptor 3 binds the B cell survival factor BAFF ligand through a discrete surface loop and promotes processing of NF-kappaB2

Immunity. 2002 Oct;17(4):515-24. doi: 10.1016/s1074-7613(02)00425-9.


The TNF-like ligand BAFF/BLyS is a potent survival factor for B cells. It binds three receptors: TACI, BCMA, and BR3. We show that BR3 signaling promotes processing of the transcription factor NF-kappaB2/p100 to p52. NF-kappaB2/p100 cleavage was abrogated in B cells from A/WySnJ mice possessing a mutant BR3 gene, but not in TACI or BCMA null B cells. Furthermore, wild-type mice injected with BAFF-neutralizing BR3-Fc protein showed reduced basal NF-kappaB2 activation. BR3-Fc treatment of NZB/WF1 mice, which develop a fatal lupus-like syndrome, inhibited NF-kappaB2 processing and attenuated the disease process. Since inhibiting the BR3-BAFF interaction has therapeutic ramifications, the ligand binding interface of BR3 was investigated and found to reside within a 26 residue core domain. When stabilized within a structured beta-hairpin peptide, six of these residues were sufficient to confer binding to BAFF.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoptosis
  • B-Cell Activating Factor
  • B-Cell Activation Factor Receptor
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism*
  • Binding Sites
  • Cell Line
  • Female
  • Ligands
  • Lupus Erythematosus, Systemic / immunology
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred A
  • Mice, Inbred C57BL
  • Mice, Inbred NZB
  • Mice, Knockout
  • Mice, Mutant Strains
  • Models, Molecular
  • Molecular Sequence Data
  • NF-kappa B / metabolism*
  • NF-kappa B p52 Subunit
  • Protein Processing, Post-Translational
  • Protein Structure, Tertiary
  • Receptors, Tumor Necrosis Factor / chemistry
  • Receptors, Tumor Necrosis Factor / genetics
  • Receptors, Tumor Necrosis Factor / metabolism*
  • Signal Transduction
  • Tumor Necrosis Factor-alpha / metabolism*


  • B-Cell Activating Factor
  • B-Cell Activation Factor Receptor
  • Ligands
  • Membrane Proteins
  • NF-kappa B
  • NF-kappa B p52 Subunit
  • Receptors, Tumor Necrosis Factor
  • Tnfrsf13c protein, mouse
  • Tnfsf13b protein, mouse
  • Tumor Necrosis Factor-alpha

Associated data

  • PDB/1MPV