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.
Department of Pathology, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07103, USA.
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M
Zhang
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SY
Chong
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ES
Raveche
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