Canonical NF-kappaB activity, dispensable for B cell development, replaces BAFF-receptor signals and promotes B cell proliferation upon activation

Immunity. 2006 Jun;24(6):729-39. doi: 10.1016/j.immuni.2006.04.005.

Abstract

The maintenance of mature B cells hinges on signals emitted from the BAFF-R cell-surface receptor, but the nature of these signals is incompletely understood. Inhibition of canonical NF-kappaB transcription factor activity through ablation of the essential scaffold protein NEMO arrests B cell development at the same stage as BAFF-R deficiency. Correspondingly, activation of this pathway by constitutively active IkappaB Kinase2 renders B cell survival independent of BAFF-R:BAFF interactions and prevents proapoptotic PKCdelta nuclear translocation. In addition, canonical NF-kappaB activity mediates differentiation and proper localization of follicular and marginal zone B cells in the absence of BAFF-R, but not CD19. By replacing BAFF-R signals, constitutive canonical NF-kappaB signaling, a hallmark of various B cell lymphomas, causes accumulation of resting B cells and promotes their proliferation and survival upon activation, but does not per se induce lymphomagenesis. Therefore, canonical NF-kappaB activity can substitute for BAFF-R signals in B cell development and pathogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Animals
  • Antigens, CD19 / genetics
  • Antigens, CD19 / metabolism
  • B-Cell Activation Factor Receptor
  • B-Lymphocytes / immunology*
  • Cell Nucleus / enzymology
  • Cell Proliferation
  • Hyperplasia
  • I-kappa B Kinase / genetics
  • I-kappa B Kinase / physiology*
  • Lymphocyte Activation
  • Lymphoma, B-Cell / genetics
  • Lymphoma, B-Cell / immunology*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Mutant Strains
  • NF-kappa B / metabolism*
  • Protein Kinase C-delta / analysis
  • Protein Kinase C-delta / metabolism
  • Receptors, Tumor Necrosis Factor / genetics
  • Receptors, Tumor Necrosis Factor / metabolism*
  • Spleen / pathology

Substances

  • Antigens, CD19
  • B-Cell Activation Factor Receptor
  • Membrane Proteins
  • NF-kappa B
  • Receptors, Tumor Necrosis Factor
  • Tnfrsf13c protein, mouse
  • I-kappa B Kinase
  • Protein Kinase C-delta