BAFF-driven NLRP3 inflammasome activation in B cells

Ken-Hong Lim, Lih-Chyang Chen, Kate Hsu, Chia-Ching Chang, Chia-Yu Chang, Chen-Wei Kao, Yi-Fang Chang, Ming-Chih Chang, Caleb Gonshen Chen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

BAFF supports B-cell survival and homeostasis by activating the NF-kappa B pathway. While NF-kappa B is also involved in the priming signal of NLRP3 inflammasome, the role of BAFF in NLRP3 inflammasome regulation is unknown. Here we report BAFF engagement to BAFF receptor elicited both priming and activating signals for NLRP3 inflammasomes in primary B cells and B lymphoma cell lines. This induction of NLRP3 inflammasomes by BAFF led to increased NLRP3 and IL-1 beta expression, caspase-1 activation, IL-1 beta secretion, and pyroptosis. Mechanistically, BAFF activated NLRP3 inflammasomes by promoting the association of cIAP-TRAF2 with components of NLRP3 inflammasomes, and by inducing Src activity-dependent ROS production and potassium ion efflux. B-cell receptor (BCR) stimulation on the Lyn signaling pathway inhibited BAFF-induced Src activities and attenuated BAFF-induced NLRP3 inflammasome activation. These findings reveal an additional function of BAFF in B-cell homeostasis that is associated with BCR activities.

Original languageEnglish
Article number820
Number of pages13
JournalCell Death and Disease
Volume11
Issue number9
DOIs
StatePublished - 1 Oct 2020

Keywords

  • NF-KAPPA-B
  • SIGNAL-TRANSDUCTION
  • TYROSINE KINASE
  • LYN KINASE
  • RECEPTOR
  • SURVIVAL
  • MECHANISM
  • APOPTOSIS
  • CASPASES
  • DISEASE

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