CCL19 and CXCL13 synergistically regulate interaction between B cell acute lymphocytic leukemia CD23+CD5+ B Cells and CD8+ T cells.
Interacting with T cells, cytokine-producing B cells play a critical protective role in autoimmune diseases. However, the interaction between malignant B and T cells remains to be fully elucidated. In a previous study, we have reported that ligation of CCL19-CCR7 and CXCL13-CXCR5 activates paternally expressed gene 10 (PEG10), resulting in an enhancement of apoptotic resistance in B-cell acute lymphocytic leukemia (B-ALL) CD23+CD5+ B cells. Here, we report that B-ALL CD23+CD5+ B cells produce IL-10 at high level, which can be further elevated by costimulation with CCL19 and CXCL13. CCL19/CXCL13-activated B-ALL CD23+CD5+ B cells, in turn, increase IL-10 expression in syngeneic CD8+ T cells in a B cell-derived IL-10-dependent manner and requiring a cell-cell contact. IL-10 secreted from B-ALL CD23+CD5+ B cells in vitro impairs tumor-specific CTL responses of syngeneic CD8+ T cells. The impairment of cytotoxicity of syngeneic CD8+ T cells is escalated by means of CCL19/CXCL13-induced up-regulation of IL-10 from B-ALL CD23+CD5+ B cells. Moreover, using a short hairpin RNA to knockdown PEG10, we provide direct evidence that increased expression of PEG10 in B-ALL CD23+CD5+ B cells is involved in malignant B-T cell interaction, contributing to the up-regulation of IL-10 expression, as well as to the impairment of cytotoxicity of syngeneic CD8+ T cells. Thus, malignant B-ALL CD23+CD5+ B cells play an immunoregulatory role in controlling different inflammatory cytokine expressions. IL-10 may be one of the critical cellular factors conferring B-ALL CD23+CD5+ B cells to escape from host immune surveillance.
Wang
Xingbing
X
Department of Hematology, Anhui Medical University Affiliated Provincial Hospital, Hefei, China.
Yuling
He
H
Yanping
Jiang
J
Xinti
Tan
T
Yaofang
Yang
Y
Feng
Yu
Y
Ruijin
Xiao
X
Li
Wang
W
Lang
Chen
C
Jingyi
Liu
L
Zhiqing
Tang
T
Jingping
Ouyang
O
Bing
Xia
X
Li
Qiao
Q
Chang
Alfred E
AE
Sun
Zimin
Z
Youxin
Jin
J
Jinquan
Tan
T
D000293:Adolescent; D000328:Adult; D051017:Apoptosis Regulatory Proteins; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002051:Burkitt Lymphoma / Q000276:immunology*; D018956:CD5 Antigens / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D054415:Chemokine CCL19 / Q000494:pharmacology / Q000502:physiology*; D054382:Chemokine CXCL13 / Q000494:pharmacology / Q000502:physiology*; D002648:Child; D002675:Child, Preschool; D003602:Cytotoxicity, Immunologic; D004268:DNA-Binding Proteins; D005260:Female; D006801:Humans; D007157:Immunologic Surveillance / Q000276:immunology*; D016753:Interleukin-10 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011506:Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D016601:RNA-Binding Proteins; D017455:Receptors, IgE / Q000032:analysis; D015854:Up-Regulation
D051017:Apoptosis Regulatory Proteins; D018956:CD5 Antigens; C110663:CXCL13 protein, human; D054415:Chemokine CCL19; D054382:Chemokine CXCL13; D004268:DNA-Binding Proteins; C432965:PEG10 protein, human; D011506:Proteins; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D017455:Receptors, IgE; D016753:Interleukin-10