CD40 Co-stimulation Inhibits Sustained BCR-induced Ca2+ Signaling in Response to Long-term Antigenic Stimulation of Immature B Cells.
10.4196/kjpp.2011.15.3.179
- Author:
Yen Hoang NGUYEN
1
;
Ki Young LEE
;
Tae Jin KIM
;
Sung Joon KIM
;
Tong Mook KANG
Author Information
1. Department of Physiology, SBRI, Sungkyunkwan University School of Medicine, Suwon 440-746, Korea. tongmkang@skku.edu
- Publication Type:Original Article
- Keywords:
B cell receptor;
Ca2+;
CD40;
Reactive oxygen species;
WEHI-231
- MeSH:
Acetylcysteine;
Apoptosis;
B-Lymphocytes;
Cell Cycle Checkpoints;
Phospholipase C gamma;
Precursor Cells, B-Lymphoid;
Reactive Oxygen Species
- From:The Korean Journal of Physiology and Pharmacology
2011;15(3):179-187
- CountryRepublic of Korea
- Language:English
-
Abstract:
Regulation of B cell receptor (BCR)-induced Ca2+ 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 [Ca2+]i was followed by spontaneous recovery to control level within 24 hr. The recovery of Ca2+ signaling in WEHI-231 cells was not due to restoration of internalized receptor but instead to an increase in the levels of PLCgamma2 and IP3R-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 Ca2+ signaling. CD40 co-stimulation also enhanced BCR internalization and reduced expression of PLCgamma2 and IP3R-3. Pre-treatment of WEHI-231 cells with the antioxidant N-acetyl-L-cysteine (NAC) strongly inhibited CD40-mediated prevention of the recovery of Ca2+ 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 [Ca2+]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 Ca2+ signaling.
