Direct B-cell stimulation by peripheral blood monocyte-derived dendritic cells in idiopathic thrombocytopenic purpura patients.
OBJECTIVE
Dendritic cells (DCs) play a major role in regulating lymphocytes. The emergence of antiplatelet autoantibodies remains the central pathogenetic mechanism in idiopathic thrombocytopenic purpura (ITP); defective DC functions have been implicated in ITP. The purpose of this study was to assess the contribution of DCs to B-cell hyperactivity in ITP patients.


METHODS
Ten ITP patients were studied before treatment (group untreated) and after treatment (group treated ) with improvement. We compared the effects of monocyte-derived DC from ITP and healthy control (group control) on naive B cells in the presence of lipopolysaccharide, or anti-CD40. We measured the proliferation, antibody production, and expression of activation markers for B cells, as well as DC-secreted B-cell activating factor (BAFF) production. We also measured the serum BAFF level in ITP patients and control. The role of DC-produced BAFF was evaluated with anti-BAFF.


RESULTS
Lipopolysaccharide, or anti-CD40, stimulated DCs from group untreated increased B-cell proliferation and antibody production as compared with DCs from group treated and group control. Cell-to-cell contact was not necessary for the augmented effect of the ITP DCs. Anti-CD40 treatment induced a higher production of BAFF in group untreated DCs. Serum BAFF levels, supernatant BAFF from anti-CD40-activated DCs, and BAFF mRNA expression of anti-CD40-activated DCs in group untreated were significantly higher than that in group treated and group control. In ITP patients, there was positive correlation among serum BAFF, supernatant BAFF, and BAFF mRNA levels, and there was negative correlation between serum BAFF, supernatant BAFF, BAFF mRNA levels, and blood platelet count. Blocking BAFF abrogated the effects of ITP DCs on naive B partially.


CONCLUSIONS
Activated monocyte-derived DCs from ITP patients directly increase B-cell effector functions; this effect depends on soluble factors released by activated DCs and cell-to-cell contact. This might play an important role in the antibody production in ITP. DC-secreted BAFF is involved and might contribute to disease development.
Zhou
Zhenhai
Z
Department of Hematology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080 Guangdong Province, People's Republic of China. zhouship@yahoo.com.cn
Li
Xiaoyin
X
Li
Juan
J
Su
Chang
C
Zhuang
Lan
L
Luo
Shaokai
S
Zhang
Ling
L
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D001323:Autoantibodies / Q000276:immunology / Q000378:metabolism; D053264:B-Cell Activating Factor / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D001792:Blood Platelets / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D009000:Monocytes / Q000473:pathology; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000097:blood / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D053264:B-Cell Activating Factor; D019013:CD40 Antigens; D008070:Lipopolysaccharides; D012333:RNA, Messenger; C505719:TNFSF13B protein, human