CD72 stimulation modulates anti-IgM induced apoptotic signaling through the pathway of NF-kappaB, c-Myc and p27(Kip1).
Engagement of mIgM induces G1 arrest and apoptosis in immature B cells. The biochemical mechanism(s) regulating the cell death process are poorly understood. Cross-linking of CD72 (a B cell co-receptor) with anti-CD72 antibody was shown to protect B cells from apoptosis. We investigated the molecular mechanism involved in apoptosis preventing signaling mediated by CD72 ligation using a derivative (WEHIdelta) of the WEHI231 cell line which is representative of immature B cells. Apoptotic WEHIdelta cells following cross-linking of mIgM demonstrate a dramatic loss of c-Myc protein after transient up-regulation. In contrast, pre-ligation of CD72 was able to sustain c-Myc expression after transient up-regulation. Cross-linking of mIgM of WEHIdelta cells causes accumulation of the Cdk inhibitor, p27(Kip1). CD72 pre-ligation was shown to inhibit the accumulation of p27(Kip1) protein. Moreover, NF-kappaB activity was not suppressed in WEHIdelta cells after mIgM cross-linking when the cells were pre-treated with anti-CD72 antibody. These results strongly suggest that the apoptosis preventing signal evoked by CD72 ligation is delivered through the pathway of NF-kappaB, c-Myc, p27(Kip1) and cyclin.
Fujiwara
Naruyoshi
N
Research Institute for Biological Sciences, Tokyo University of Science, Japan.
Fusaki
Noemi
N
Hozumi
Nobumichi
N
D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology*; D017209:Apoptosis; D001402:B-Lymphocytes / Q000502:physiology*; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000378:metabolism; D016193:G1 Phase; D007075:Immunoglobulin M / Q000276:immunology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D016213:Cyclins; D007075:Immunoglobulin M; D016328:NF-kappa B; D016271:Proto-Oncogene Proteins c-myc; D011947:Receptors, Antigen, B-Cell; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27