CXC chemokine ligand 13 and CC chemokine ligand 19 cooperatively render resistance to apoptosis in B cell lineage acute and chronic lymphocytic leukemia CD23+CD5+ B cells.
CXCL13/CXCR5 and CCL19/CCR7 play a quite important role in normal physiological conditions, but the functions of both chemokine/receptor pairs in pathophysiological events are not well-investigated. We have investigated expression and functions of CXCL13/CXCR5 and CCL19/CCR7 in CD23+CD5+ and CD23+CD5- B cells from cord blood (CB) and patients with B cell lineage acute or chronic lymphocytic leukemia (B-ALL or B-CLL). CXCR5 and CCR7 are selectively expressed on B-ALL, B-CLL, and CB CD23+CD5+ B cells at high frequency, but not on CD23+CD5- B cells. Although no significant chemotactic responsiveness was observed, CXCL13 and CCL19 cooperatively induce significant resistance to TNF-alpha-mediated apoptosis in B-ALL and B-CLL CD23+CD5+ B cells, but not in the cells from CB. B-ALL and B-CLL CD23+CD5+ B cells express elevated levels of paternally expressed gene 10 (PEG10). CXCL13 and CCL19 together significantly up-regulate PEG10 expression in the same cells. We have found that CXCL13 and CCL19 together by means of activation of CXCR5 and CCR7 up-regulate PEG10 expression and function, subsequently stabilize caspase-3 and caspase-8 in B-ALL and B-CLL CD23+CD5+ B cells, and further rescue the cells from TNF-alpha-mediated apoptosis. Therefore, we suggest that normal lymphocytes, especially naive B and T cells, use CXCL13/CXCR5 and CCL19/CCR7 for migration, homing, maturation, and cell homeostasis as well as secondary lymphoid tissues organogenesis. In addition, certain malignant cells take advantages of CXCL13/CXCR5 and CCL19/CCR7 for infiltration, resistance to apoptosis, and inappropriate proliferation.
Chunsong
Hu
H
Department of Immunology, School of Basic Medical Sciences, Anhui Medical University, Hefei, China.
Yuling
He
H
Li
Wang
W
Jie
Xiong
X
Gang
Zhou
Z
Qiuping
Zhang
Z
Qingping
Gao
G
Kejian
Zhang
Z
Li
Qiao
Q
Chang
Alfred E
AE
Youxin
Jin
J
Jinquan
Tan
T
D017209:Apoptosis / Q000276:immunology*; D051017:Apoptosis Regulatory Proteins; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002051:Burkitt Lymphoma / Q000276:immunology* / Q000473:pathology; D018956:CD5 Antigens / Q000096:biosynthesis; D019070:Cell Lineage / Q000276:immunology; D054415:Chemokine CCL19; D054382:Chemokine CXCL13; D019742:Chemokines, CC / Q000502:physiology*; D019743:Chemokines, CXC / Q000502:physiology*; D004268:DNA-Binding Proteins; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology* / Q000473:pathology; D018655:Lymphocyte Count; D011506:Proteins / Q000378:metabolism / Q000502:physiology; D016601:RNA-Binding Proteins; D054400:Receptors, CCR7; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine / Q000096:biosynthesis; D017455:Receptors, IgE / Q000096:biosynthesis
D051017:Apoptosis Regulatory Proteins; C515460:CCL19 protein, human; C515370:CCR7 protein, human; D018956:CD5 Antigens; 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; D017455:Receptors, IgE