PEG10 Activation by Co-Stimulation of CXCR5 and CCR7 Essentially Contributes to Resistance to Apoptosis in CD19^(+)CD34^(+) B Cells from Patients with B Cell Lineage Acute and Chronic Lymphocytic Leukemia

We investigated CD19^+CD34^+ and CD19^+CD34 B cells from cord blood (CB) and typical patients with B cell lineage acute and chronic lymphocytic leukemia (B-ALL and B-CLL) in terms of expression and functions of CXCR5/CXCL13 and CCR7/CCL19.CXCR5 and CCR7 were selectively frequent expressed on B-ALL,B-CLL and CB CD19^+CD34^+ B cells,but not on CD19^+CD34 B cells.Instead of induction of impressive chemotactic responsiveness,CXCL13 and CCL19 together induced significant resistance to TNF-α-mediated apoptosis in B-ALL and B-CLL but not CB CD19^+CD34^+ B cells.B-ALL and B-CLL CD19^+CD34^+ B cells expressed elevated level of Paternally Expressed Gene 10 (PEG10),and CXCL13 and CCL19 together significantly up-regulated PEG10 expression in the cells.We found that CXCL13 and CCL19 together by means of activation of CXCR5 and CCR7 up-regulated PEG10 expression and function,subsequent stabilized caspase-3 and caspase-8 in B-ALL and B-CLL CD19^+CD34^+ B cells,and rescued the cells from TNF-α-mediated apoptosis.We suggested that normal lymphocytes,especially naive B and T cells,utilized CXCR5/CXCL13 and CCR7/CCL19 for migration,homing,maturation,and cell homeostasis as well as secondary lymphoid tissues organogenesis. Meanwhile certain malignant cells took advantages of CXCR5/CXCL13 and CCR7/CCL19 for infiltration, resistance to apoptosis,and inappropriate proliferation.Cellular & Molecular Immunology.2004;1(4):280-294.