title: CD40 Co-stimulation Inhibits Sustained BCR-induced Ca Signaling in Response to Long-term Antigenic Stimulation of Immature B Cells.
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 α-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 PLCγ2 and IP(3)R-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 PLCγ2 and IP(3)R-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 α-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.
authors.affiliation: Department of Physiology, SBRI, Sungkyunkwan University School of Medicine, Suwon 440-746, Korea.
authors.forename: Yen Hoang
authors.initials: YH
authors.lastname: Nguyen
authors.forename: Ki-Young
authors.initials: KY
authors.lastname: Lee
authors.forename: Tae Jin
authors.initials: TJ
authors.lastname: Kim
authors.forename: Sung Joon
authors.initials: SJ
authors.lastname: Kim
authors.forename: Tong Mook
authors.initials: TM
authors.lastname: Kang