BCR-Induced Ca2+ Signals Dynamically Tune Survival, Metabolic Reprogramming, and Proliferation of Naive B Cells

Corbett T. Berry, Xiaohong Liu, Arpita Myles, Satabdi Nandi, Youhai H. Chen, Uri Hershberg, Igor E. Brodsky, Michael P. Cancro, Christopher J. Lengner, Michael J. May, Bruce D. Freedman

Research output: Contribution to journalArticlepeer-review


B cell receptor (BCR) engagement induces naive B cells to differentiate and perform critical immune-regulatory functions. Acquisition of functional specificity requires that a cell survive, enter the cell cycle, and proliferate. We establish that quantitatively distinct Ca2+ signals triggered by variations in the extent of BCR engagement dynamically regulate these transitions by controlling nuclear factor κB (NF-κB), NFAT, and mTORC1 activity. Weak BCR engagement induces apoptosis by failing to activate NF-κB-driven anti-apoptotic gene expression. Stronger signals that trigger more robust Ca2+ signals promote NF-κB-dependent survival and NFAT-, mTORC1-, and c-Myc-dependent cell-cycle entry and proliferation. Finally, we establish that CD40 or TLR9 costimulation circumvents these Ca2+-regulated checkpoints of B cell activation and proliferation. As altered BCR signaling is linked to autoimmunity and B cell malignancies, these results have important implications for understanding the pathogenesis of aberrant B cell activation and differentiation and therapeutic approaches to target these responses.

Original languageEnglish
Article number107474
JournalCell Reports
Issue number2
StatePublished - 14 Apr 2020

Bibliographical note

Publisher Copyright:
© 2020 The Authors


  • Bcl-xL
  • CD40
  • NFAT
  • Orai1
  • STIM1
  • apoptosis
  • c-Myc
  • c-Rel
  • mTORC1
  • nuclear factor kappa B

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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