Responsiveness of peripheral blood B cells to recombinant CD40 ligand in patients with systemic lupus erythematosus
Responsiveness of peripheral blood B cells to recombinant CD40 ligand in patients with systemic lupus erythematosus
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DOI：
10.1191/096120399678847678
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发表时间：
1999-01-01
期刊：
影响因子：
2.6
通讯作者：
Kashiwazaki, S
中科院分区：
文献类型：
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作者：
Harigai, M;Hara, M;Kashiwazaki, S
目的：为探讨系统性红斑狼疮（SLE）患者B细胞过度活化中CD 40/CD 40配体系统的免疫病理学意义，采用流式细胞术检测SLE患者B细胞表面CD 40的表达及功能。H-3 - TdR掺入法测定B细胞DNA合成。结果：SLE患者外周血B细胞CD 40表达与正常对照组无显著性差异。重组CD 40配体-亮氨酸拉链融合蛋白（CD 40 L-LZ）能显著增加SLE和正常B细胞的~ 3 H-TdR掺入（P < 0.01）。SLE患者B细胞H-3 - TdR掺入量在无刺激（P < 0.001）和有CD 40 L-LZ刺激（P < 0.05）时均显著低于正常对照组。活动期SLE B细胞自发产生的总IgG显著高于正常B细胞（P < 0.05）。CD 40 L-LZ能显著增加SLE B细胞总IgG的产生（P < 0.05），但对正常B细胞无明显影响。活性SLE B细胞自发产生IgG抗dsDNA和ISG抗ssDNA抗体。CD 40 L-LZ可显著增加SLE B细胞产生上述自身抗体（P < 0.05）。正常对照的B细胞不自发产生这些自身抗体，也不响应于CD 40 L-LZ.Conclusion：这些研究结果表明，通过CD 40信号转导在B细胞增殖和自身抗体的产生在人类SLE中起着重要作用。
Objective: To investigate the immunopathological significance of CD40/CD40 ligand system for B cell hyperactivation in SLE patients, the expression and the function of CD40 on B cells were compared with those of normal controls.Methods: Expression of CD40 was evaluated by flow cytometry. DNA synthesis of B cells were measured by H-3 - TdR incorporation. Antibody production was assessed by ELISA.Results: There was no significant difference between SLE and normal controls in CD40 expression on peripheral blood B cells. Recombinant CD40 ligand-leucine zipper fusion protein (CD40L-LZ) significantly enhanced 3H - TdR incorporation by both SLE and normal B cells (P < 0.01). H-3 - TdR incorporation of SLE B cells without stimuli (P < 0.001) and with CD40L-LZ stimulation (P < 0.05) were significantly lower in SLE patients compared with normal controls. Active SLE B cells spontaneously produced significantly larger amounts of total IgG than normal B cells (P < 0.05). CD40L-LZ significantly increased the production of total IgG by SLE B cells (P < 0.05), but not by normal B cells. Active SLE B cells spontaneously produced IgG anti-dsDNA and ISG anti-ssDNA antibodies. CD40L-LZ significantly increased the production of these autoantibodies by SLE B cells (P < 0.05). B cells from normal controls do not produce these autoantibodies spontaneously nor in response to CD40L-LZ.Conclusion: These findings indicate that signalling via CD40 plays an important role in B cell proliferation and autoantibody production in human SLE.