| Chemokines and their receptors are known as principal regulators of lymphocyte and dendritic cell (DC) migration in immune system homeostasis, infection and inflammation. They are closely related to tumor, asthema, infection of HIV and other inflammation diseases or autoimmune diseases. Here we investigated acute and chronic B lymphocytic leukemia (B-ALL and B-CLL) in terms of expression and functions of chemokines and their receptors, and explored the pathogenesis of B lymphocytic leukemia. Flow cytometry is performed to select B-ALL and B-CLL cells and detect the expression of chemokine receptors on the surface of B-ALL and B-CLL cells. The chemotaxis of corresponding chemokines in B-ALL and B-CLL CD19~+CD34~+B cells was detected by chemotaxis assay. The apoptosis of CD19~+CD34~+B and CD19~+CD34~-B cells of B-ALL and B-CLL induced by TNF-a was detected by flow cytometric analysis in the presence of chemokines.Flow cytometric assay showed CXCR5 and CCR7 were selectively frequent expressed on B-ALL and B-CLL CD19~+CD34~+B cells: The expression of CXCR5 on the CD19~+CD34~+B cells and CD19~+CD34B cells in B-ALL was 85% and 31%, respectively. The expression of CXCR5 on the CD19~+CD34~+B cells and CD19~+CD34 B cells in B-CLL was 51% and 11%, respectively. The expression of CCR7 on the CD19~+CD34~+B cells and CD19~+CD34"B cells in B-ALL was 79% and 28%, respectively. The expression of CCR7 on the CD19~+CD34~+B cells and CD19~+CD34~-B cells in B-CLL was 45% and 12%, respectively. CXCR5 and CCR7 were at rather low level on CD19~+ B cells from normal peripheral blood, whereas they were expressed at similar levels on the CD19~+CD34~+B and CD19~+CD34~-B cells from cord blood, which was between the level in normal peripheral blood group and the level in B-ALL and B-CLL group. Other CXC and CC chemokine receptors, such as CXCR3, CXCR6, CCR4 and CCR9 were showed no differences among four groups of cell sources. The chemotaxis assay indicated that CXCL13 and CCL19 induced weak chemotaxis in B-ALL and B-CLL CD19~+CD34~+B cells: When the concentration of chemokines was 1×10~2 ng/ml, the chemotatic index(C. I. ) was 3.35, 2.07and 2.15 in CCL3-treated group, CXCL13-treated group and CCL19-treated group, respectively. Flow cytometric analysis revealed that the number of apoptotic cells treated with TNF-a showed no significant differences among four groups of cell sources. The number of apoptotic cells treated with TNF-a in the presence of CXCL13 or CCL19 alone showed no significant differences among four groups of cell sources, either. The number of apoptotic and necrotic cells were significantly decreased in culture of B-ALL and B-CLL CD19+CD34+B cells* in the presence of CXCL13/BCA-1 and CCL19/ELC together. B-ALL and B-CLL CD19+CD34+B cells were pretreated with pertussis toxin (PT), a PKC pathway inhibitor, wortmannin(a PI-3 kinase inhibitor) or PD98059(a MAPK inhibitor), the results showed that only pertussis toxin significantly inhibited apoptotic protection effect of co-stimulation with CXCL13 and CCL19 in BALL CD 19+CD34+B cells. Neither PD98059 nor wortmannin did inhibit apoptotic protection effect in B-ALL CD19+CD34+B cells.CXCR5 and CCR7 were selectively frequently expressed on B-ALL and B-CLL CD19+CD34+B cells, suggesting their role in the development of B-ALL^flB-CLL. The corresponding legand of CXCR5 and CCR7 is CXCL13 and CCL19, respectively. CXCL13 and CCL19 induce weak chemotaxis in B-ALL and B-CLL CD19+CD34+B cells, which suggest that chemotactic functions are not important for CXCR5-CXCL13 pair and CCR7-CCL19 pairs in B-ALL and B-CLL. CXCL13 and CCL19 together induce significant resistance to TNF-cc-mediated apoptosis in B-ALL and B-CLL CD19+CD34+B cells, which may be a cue that CXCR5/CXCL13 and CCR7/CCL19 play a pivotal role in the malignant proliferation of B-ALL and B-CLL CD19+CD34+B cells. Their effects can be inhibited by a PKC pathway inhibitor, indicating that CXCR5-CXCL13 pair and CCR7-CCL19 pair together selectively rescue B-ALL and B-CLL CD19+CD34+B cells from TNF-a-mediated apoptosis via PKC pathway and thus contribute to the malignant proliferation of B-ALL and B-CLL CD19+CD34+B cells.
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