The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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CD40 Co-stimulation Inhibits Sustained BCR-induced $Ca^{2+}$ Signaling in Response to Long-term Antigenic Stimulation of Immature B Cells

  • Nguyen, Yen Hoang (Department of Physiology, SBRI, Sungkyunkwan University School of Medicine) ;
  • Lee, Ki-Young (Department of Molecular Cell Biology, SBRI, Sungkyunkwan University School of Medicine) ;
  • Kim, Tae-Jin (Department of Molecular Cell Biology, SBRI, Sungkyunkwan University School of Medicine) ;
  • Kim, Sung-Joon (Department of Physiology, Seoul National University College of Medicine) ;
  • Kang, Tong-Mook (Department of Physiology, SBRI, Sungkyunkwan University School of Medicine)
  • Received : 2011.05.17
  • Accepted : 2011.05.31
  • Published : 2011.06.30
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Abstract

Regulation of B cell receptor (BCR)-induced $Ca^{2+}$ signaling by CD40 co-stimulation was compared in long-term BCR-stimulated immature (WEHI-231) and mature (Bal-17) B cells. In response to long-term pre-stimulation of immature WEHI-231 cells to ${\alpha}$-IgM antibody (0.5~48 hr), the initial transient decrease in BCR-induced $[Ca^{2+}]_i$ was followed by spontaneous recovery to control level within 24 hr. The recovery of $Ca^{2+}$ signaling in WEHI-231 cells was not due to restoration of internalized receptor but instead to an increase in the levels of $PLC{\gamma}2$ and $IP_3R-3$. CD40 co-stimulation of WEHI-231 cells prevented BCR-induced cell cycle arrest and apoptosis, and it strongly inhibited the recovery of BCR-induced $Ca^{2+}$ signaling. CD40 co-stimulation also enhanced BCR internalization and reduced expression of $PLC{\gamma}2$ and $IP_3R-3$. Pre-treatment of WEHI-231 cells with the antioxidant N-acetyl-L-cysteine (NAC) strongly inhibited CD40-mediated prevention of the recovery of $Ca^{2+}$ signaling. In contrast to immature WEHI-231 cells, identical long-term ${\alpha}$-IgM pre-stimulation of mature Bal-17 cells abolished the increase in BCR-induced $[Ca^{2+}]_i$, regardless of CD40 co-stimulation. These results suggest that CD40-mediated signaling prevents antigen-induced cell cycle arrest and apoptosis of immature B cells through inhibition of sustained BCR-induced $Ca^{2+}$ signaling.

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References

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