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aberrant cd40-induced nf-κb activation in human lupus b lymphocytes异常cd40-induced nf-κb人类狼疮b淋巴细胞活化
Aberrant CD40-Induced NF-kB Activation in Human
Lupus B Lymphocytes
1 1 1 1 1 1 1
Wen Zhang , Qun Shi , Xiaotian Xu , Hua Chen , Wei Lin , Fengchun Zhang , Xiaofeng Zeng ,
1 2 2
Xuan Zhang *, Denian Ba , Wei He
1 Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, China,
2 Department of Immunology, School of Basic Medicine, Peking Union Medical College and Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences,
No. 5, Dong Dan San Tiao, Beijing, China
Abstract
Auto-reactive B lymphocytes and its abnormal CD40 signaling play important roles in the pathogenesis of systemic lupus
erythematosus (SLE). In this study, we analyzed CD40 expression and CD40/CD154 induced activation of NF-kB signaling
pathway in B cells from SLE patients. B cells from healthy volunteers and tonsilar B cells from chronic tonsillitis were used as
negative and positive controls. Results showed CD40-induced NF-kB signaling was constitutively activated in B cells from
active lupus patients, including decreased CD40 in raft portion, increased phosphorylation and degradation of IkBa,
phosphorylation of P65, as well as increased nuclear translocation of P65, P50, c-Rel, which could be blocked by anti-CD154.
CD154 stimulation could induce further phosphorylation and degradation of IkBa, as well as phosphorylation of P65 and
nuclear translocation of P65. In addition, CD40-induced kinase activities in B cells from lupus patients mimicked that of
tonsil B cells, in that IKKa/ b were more activated compared to normal B cells. CD40-induced NF-kB activity was blocked by
both IkB ph
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