We investigated CD19~+CD34~+ and CD19~+CD34 B cells from cord blood (CB) and typical patients with B celllineage acute and chronic lymphocytic leukemia (B-ALL and B-CLL) in terms of expression and functions ofCXCR5/CXCL13 and CCR7/CCL19.CXCR5 and CCR7 were selectively frequent expressed on B-ALL,B-CLLand CB CD19~+CD34~+ B cells,but not on CD19~+CD34 B cells.Instead of induction of impressive chemotacticresponsiveness,CXCL13 and CCL19 together induced significant resistance to TNF-α-mediated apoptosis inB-ALL and B-CLL but not CB CD19~+CD34~+ B cells.B-ALL and B-CLL CD19~+CD34~+ B cells expressed elevatedlevel of Paternally Expressed Gene 10 (PEG10),and CXCL13 and CCL19 together significantly up-regulatedPEG10 expression in the cells.We found that CXCL13 and CCL19 together by means of activation of CXCR5and CCR7 up-regulated PEG10 expression and function,subsequent stabilized caspase-3 and caspase-8 inB-ALL and B-CLL CD19~+CD34~+ B cells,and rescued the cells from TNF-α-mediated apoptosis.We suggestedthat normal lymphocytes,especially naive B and T cells,utilized CXCR5/CXCL13 and CCR7/CCL19 formigration,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. We investigated CD19 ~ + CD34 ~ + and CD19 ~ + CD34 B cells from cord blood (CB) and typical patients with B celllineage 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 most frequently 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 inB-ALL and B-CLL but not CB CD19 ~ + CD34 ~ + B cells.B-ALL and B-CLL CD19 ~ + CD34 ~ + B cells expressed elevatedlevel 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, subsequently stabilized caspase-3 and caspase- 8 inB-ALL and B-CLL CD19 ~ + CD34 ~ + B cells, and rescued the cells from TNF-α-mediated apoptotic †, suggesting that normal lymphocytes, particularly naive B and T cells, utilize CXCR5 / CXCL13 and CCR7 / CCL19 form migration, homing, maturation, and cell homeostasis as well as secondary lymphoid tissues organogenesis. Certain certain malignant cells have advantages of CXCR5 / CXCL13 and CCR7 / CCL19 for infiltration, resistance to apoptosis, and inappropriate proliferation. Cellular & Molecular Immunology. 2004; 1 (4): 280-294.