title: 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.
abstract: 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-alpha-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-alpha-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.
authors.affiliation: Department of Immunology, College of Basic Medical Sciences, Anhui Medical University, Hefei 230032, China.
authors.forename: Chunsong
authors.initials: C
authors.lastname: Hu
authors.forename: Jei
authors.initials: J
authors.lastname: Xiong
authors.forename: Linjei
authors.initials: L
authors.lastname: Zhang
authors.forename: Baojun
authors.initials: B
authors.lastname: Huang
authors.forename: Qiuping
authors.initials: Q
authors.lastname: Zhang
authors.forename: Qun
authors.initials: Q
authors.lastname: Li
authors.forename: Mingzhen
authors.initials: M
authors.lastname: Yang
authors.forename: Yaou
authors.initials: Y
authors.lastname: Wu
authors.forename: Qun
authors.initials: Q
authors.lastname: Wu
authors.forename: Qian
authors.initials: Q
authors.lastname: Shen
authors.forename: Qingping
authors.initials: Q
authors.lastname: Gao
authors.forename: Kejian
authors.initials: K
authors.lastname: Zhang
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Sun
authors.forename: Junyan
authors.initials: J
authors.lastname: Liu
authors.forename: Youxin
authors.initials: Y
authors.lastname: Jin
authors.forename: Jinquan
authors.initials: J
authors.lastname: Tan
mesh_terms: D000328:Adult; D000368:Aged; D018941:Antigens, CD19 / Q000276:immunology*; D018952:Antigens, CD34 / Q000235:genetics / Q000276:immunology*; D017209:Apoptosis / Q000502:physiology; D051017:Apoptosis Regulatory Proteins; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000502:physiology; D020169:Caspases / Q000378:metabolism; D019070:Cell Lineage; D054415:Chemokine CCL19; D054382:Chemokine CXCL13; D019742:Chemokines, CC / Q000235:genetics / Q000276:immunology; D019743:Chemokines, CXC / Q000235:genetics / Q000276:immunology; D004268:DNA-Binding Proteins; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D015448:Leukemia, B-Cell / Q000276:immunology*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011506:Proteins / Q000235:genetics / Q000276:immunology*; D016601:RNA-Binding Proteins; D054400:Receptors, CCR7; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine / Q000235:genetics / Q000276:immunology*; D018121:Receptors, Cytokine / Q000235:genetics / Q000276:immunology*
chemical_list: D018941:Antigens, CD19; D018952:Antigens, CD34; D051017:Apoptosis Regulatory Proteins; C515460:CCL19 protein, human; C515370:CCR7 protein, human; C110663:CXCL13 protein, human; C095085:CXCR5 protein, human; D054415:Chemokine CCL19; D054382:Chemokine CXCL13; D019742:Chemokines, CC; D019743:Chemokines, CXC; D004268:DNA-Binding Proteins; C432965:PEG10 protein, human; D011506:Proteins; D016601:RNA-Binding Proteins; D054400:Receptors, CCR7; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D020169:Caspases