title: Pre-B cell antigen receptor-mediated signal inhibits CD24-induced apoptosis in human pre-B cells.
abstract: We previously reported that the cross-linking of cluster of differentiation (CD)24 induces apoptosis in Burkitt's lymphoma cells and that this phenomenon can be enhanced by a B cell Ag receptor (BCR)-mediated signal. In this study, we extend our previous observation and report that CD24 also mediated apoptosis in human precursor-B acute lymphoblastic leukemia cell lines in the pro-B and pre-B stages accompanying activation of multiple caspases. Interestingly, simultaneous cross-linking of pre-BCR clearly inhibited CD24-mediated apoptosis in pre-B cells. We also observed that mitogen-activated protein kinases (MAPKs) were involved in the regulation of this apoptotic process. Pre-BCR cross-linking induced prompt and strong activation of extracellular signal-regulated kinase 1, whereas CD24 cross-linking induced the sustained activation of p38 MAPK, following weak extracellular signal-regulated kinase 1 activation. SC68376, a specific inhibitor of p38 MAPK, inhibited apoptosis induction by CD24 cross-linking, whereas anisomycin, an activator of p38 MAPK, enhanced the apoptosis. In addition, PD98059, a specific inhibitor of MEK-1, enhanced apoptosis induction by CD24 cross-linking and reduced the antiapoptotic effects of pre-BCR cross-linking. Collectively, whether pre-B cells survive or die may be determined by the magnitude of MAPK activation, which is regulated by cell surface molecules. Our findings should be important to understanding the role of CD24-mediated cell signaling in early B cell development.
authors.affiliation: Department of Developmental Biology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Taguchi
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Kiyokawa
authors.forename: Kenichi
authors.initials: K
authors.lastname: Mimori
authors.forename: Toyo
authors.initials: T
authors.lastname: Suzuki
authors.forename: Takaomi
authors.initials: T
authors.lastname: Sekino
authors.forename: Hideki
authors.initials: H
authors.lastname: Nakajima
authors.forename: Masahiro
authors.initials: M
authors.lastname: Saito
authors.forename: Yohko U
authors.initials: YU
authors.lastname: Katagiri
authors.forename: Nobutake
authors.initials: N
authors.lastname: Matsuo
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Matsuo
authors.forename: Hajime
authors.initials: H
authors.lastname: Karasuyama
authors.forename: Junichiro
authors.initials: J
authors.lastname: Fujimoto
mesh_terms: D000911:Antibodies, Monoclonal / Q000378:metabolism; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D017209:Apoptosis / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000201:enzymology / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D002051:Burkitt Lymphoma / Q000201:enzymology / Q000276:immunology; D051927:CD24 Antigen; D020169:Caspases / Q000378:metabolism; D015536:Down-Regulation / Q000276:immunology*; D004789:Enzyme Activation / Q000276:immunology; D006801:Humans; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000201:enzymology / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D054420:Pre-B Cell Receptors; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D011947:Receptors, Antigen, B-Cell; D015398:Signal Transduction / Q000276:immunology*; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D051927:CD24 Antigen; C497889:CD24 protein, human; D008562:Membrane Glycoproteins; D054420:Pre-B Cell Receptors; D011947:Receptors, Antigen, B-Cell; D020928:Mitogen-Activated Protein Kinases; D020169:Caspases