An Intact NF-kappa B Signaling Pathway Is Required for Maintenance of Mature B Cell Subsets

Mol Immunol. 1999 Feb;36(3):187-95. doi: 10.1016/s0161-5890(99)00031-0.

Abstract

Members of the NF-kappaB/Rel transcription factor family are expressed constitutively during B cell development and are further induced by mitogen activation. Mice harboring germline disruptions in individual NF-kappaB subunits exhibit distinct defects in B lymphocyte activation and survival. However, the role of NF-kappaB in the production and maintenance of B cell subsets has been difficult to dissect in these knockout animals due to functional impairment of other immune cells. To directly address the cell autonomous requirements for NF-kappaB in humoral immune compartments, transgenic mice were generated that express a transdominant form of Ikappa-Balpha in B lineage cells. Whereas expression of the inhibitor had only modest effects on basal or LPS-induced levels of NF-kappaB, transgenic B cells were significantly impaired for cellular proliferation and NF-kappaB induction in response to B cell receptor (BCR) crosslinking. Furthermore, the trans-dominant inhibitor produced a dose-dependent reduction in the population of mature splenic B cells. This cellular defect was more pronounced in long-lived B lymphocyte subsets that recirculate to the adult bone marrow. Together, these results indicate that BCR-mediated signaling must maintain NF-kappaB levels above a stringent threshold for proper regulation of B cell homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • B-Lymphocyte Subsets / metabolism
  • B-Lymphocyte Subsets / pathology
  • B-Lymphocyte Subsets / physiology*
  • Bone Marrow
  • Cell Differentiation / immunology
  • Cells, Cultured
  • DNA-Binding Proteins / biosynthesis
  • I-kappa B Proteins*
  • Lymphocyte Activation
  • Lymphocyte Depletion
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Transgenic
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / biosynthesis
  • NF-kappa B / genetics
  • NF-kappa B / physiology*
  • Receptors, Antigen, B-Cell / physiology
  • Signal Transduction / immunology*
  • Spleen

Substances

  • DNA-Binding Proteins
  • I-kappa B Proteins
  • NF-kappa B
  • Nfkbia protein, mouse
  • Receptors, Antigen, B-Cell
  • NF-KappaB Inhibitor alpha