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-l cells, many of which demonstrate self-reactivity, The response of B-l cells to mitogen after undergoing malignant transformation is still unclear. Using our established malignant B-l cell lines derived from the NZB murine model of human CLL, we investigated the response of malignant B-l cells to the mitogen LPS, Interestingly, these malignant B-l 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-l 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. (C) 2001 Academic Press.