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.

Targeting CD24 for Treatment of Colorectal and Pancreatic Cancer by Monoclonal Antibodies or Small Interfering RNA

“…CD24 is also known to be an alternative ligand for P-selectin and thus might function in metastases shedding (14)(15)(16)(17). Anti-CD24 monoclonal antibodies (mAb) induced growth inhibition in lymphocytes precursors (18,19). We have shown that the growth of human colon and pancreatic cancer cell lines is inhibited in response to CD24 mAb in a dose-dependent and time-dependent manner and in a close association with their CD24 expression level.…”

“…Thus, recruitment of Src kinases to lipid rafts domains (26), activation of MAPKs and thus caspases (19), changes in the balance of the BCl-2 superfamily (27), or elevation of cytoplasmic calcium levels (10) was tied with the excitation of the pathway by specific antibodies in hematopoietic cells. CD24 ectopic expression in breast cancer cells resulted in increased proliferation rates and the activation of the a 3 h 1 and a 4 h 1 integrins, which induce binding to selectins, collagen, and laminin and thus cell migration (21).…”

CD24-Triggered Caspase-Dependent Apoptosis via Mitochondrial Membrane Depolarization and Reactive Oxygen Species Production of Human Neutrophils Is Impaired in Sepsis

“…In hematopoietic cells, CD24 is expressed on B cells, T cells, eosinophils, dendritic cells, and, most prominently, neutrophils (12). It has been stated that CD24 expression on T cells is required for optimal homeostatic proliferation (13), whereas several other reports showed that cross-linking of CD24 transduces apoptotic signals in other cell types (14)(15)(16). Therefore, both enhanced expression and lack of CD24 can affect cellular functions.…”

Rotavirus Infection Alters Peripheral T-Cell Homeostasis in Children with Acute Diarrhea

“…1D). Antigen receptors CD20, CD21, CD24, CD72, and CD79B influence the survival of B cells via different mechanisms, including the induction of apoptosis by the activation of multiple caspase cascades and mitogen-activated protein kinase, the activation of the alternative complement pathway and the formation of membrane attack complexes, and the regulation or modulation of B-cell receptor signaling (42,49,51). Of note, CD21 and CD72 have dual functions and are also involved in the positive regulation of B lymphocytes (23,42).…”