Involvement of cell cycle progression in survival signaling through CD40 in the B-lymphocyte line WEHI-231.
The CD40 molecule transmits a signal that abrogates apoptosis induced by ligation of the antigen receptor (BCR) in both primary B cells and B-cell lines such as WEHI-231. Expression of Bcl-xL and A1, antiapoptotic members of the Bcl-2 family, is enhanced by CD40 ligation, and is suggested to mediate CD40-induced B-cell survival. CD40 ligation also promotes cell cycle progression by increasing the levels of cyclin-dependent kinases (CDKs) required for cell cycle progression, and reducing expression of the CDK inhibitor p27(kip1). Here we demonstrate that cell cycle inhibition by retrovirus-mediated p27(kip1) expression does not modulate the levels of Bcl-xL or A1, but significantly reduces the survival of BCR-ligated WEHI-231 cells by CD40 ligation. This indicates that cell cycle progression is crucial for CD40-mediated survival of B cells.
Hirai
H
H
Laboratory of Immunology, School of Biomedical Science, and Department of Immunology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
Adachi
T
T
Tsubata
T
T
D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D015153:Blotting, Western; D019013:CD40 Antigens / Q000378:metabolism*; D002453:Cell Cycle; D002460:Cell Line; D002470:Cell Survival; D018844:Cyclin-Dependent Kinases; D004591:Electrophoresis, Polyacrylamide Gel; D005434:Flow Cytometry; D051379:Mice; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D012190:Retroviridae / Q000235:genetics; D015398:Signal Transduction
D019013:CD40 Antigens; D019253:Proto-Oncogene Proteins c-bcl-2; D018844:Cyclin-Dependent Kinases