The role of B-cell-specific activator protein in the response of malignant B-1 cells to LPS.
Chronic lymphocytic leukemia (CLL) results from the uncontrolled proliferation and accumulation of B-1 cells, many of which demonstrate self-reactivity. The response of B-1 cells to mitogen after undergoing malignant transformation is still unclear. Using our established malignant B-1 cell lines derived from the NZB murine model of human CLL, we investigated the response of malignant B-1 cells to the mitogen LPS. Interestingly, these malignant B-1 cells proliferated initially, but the proliferation rate decreased after a 48-h transition. Prolonged LPS treatment induced apoptosis and pathological differentiation. We studied possible underlying molecular mechanisms and found that the level of the DNA binding protein BSAP (B-cell-specific activator protein) was upregulated by LPS at the initial activation stage, followed by an increase in the apoptotic factor caspase-3 (CPP32) at 48 h and a subsequent decrease of BSAP at 72 h. The pathological differentiation induced by LPS was partially prevented by treatment with antisense BSAP. This study indicates that malignant B-1 cells could be driven to apoptosis and pathological differentiation when activated by the mitogen LPS, and BSAP may be an important factor in regulating these responses.
Zhang
M
M
Department of Pathology, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07103, USA.
Chong
S Y
SY
Raveche
E S
ES
D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008934:Mitogens / Q000494:pharmacology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016376:Oligonucleotides, Antisense; D051757:PAX5 Transcription Factor; D014157:Transcription Factors
D004268:DNA-Binding Proteins; D008070:Lipopolysaccharides; D008934:Mitogens; D009687:Nuclear Proteins; D016376:Oligonucleotides, Antisense; D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human; C497282:Pax5 protein, mouse; D014157:Transcription Factors; D004247:DNA