An intact NF-κB signaling pathway is required for maintenance of mature B cell subsets

Heather H. Bendall, Michael L. Sikes, Dean W. Ballard, Eugene M. Oltz

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

Members of the NF-κB/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-κB subunits exhibit distinct defects in B lymphocyte activation and survival. However, the role of NF-κB 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-κB in humoral immune compartments, transgenic mice were generated that express a transdominant form of IκBα in B lineage cells. Whereas expression of the inhibitor had only modest effects on basal or LPS- induced levels of NF-κB, transgenic B cells were significantly impaired for cellular proliferation and NF-κB 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-κB levels above a stringent threshold for proper regulation of B cell homeostasis.

Original languageEnglish
Pages (from-to)187-195
Number of pages9
JournalMolecular Immunology
Volume36
Issue number3
DOIs
StatePublished - Feb 1 1999

Keywords

  • B cell development
  • B cell homeostasis
  • B cell receptor signaling
  • NF-κB/Rel transcription factors
  • Transgenic mice

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