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     Conclusion Failure of B cells to undergo immunoglobulin isotype switch in this case is a result of mutation on the CD 40 L gene in the activated T cells and B cells may have the ability to secrete IgG. This is the first case of HIGM with X linked inheritance diagnosed at a molecular level in China.
     结论患儿B细胞可能具有正常Ig分泌功能,Ig同种型转换障碍是由于其T细胞CD40L基因缺失,并在国内首次从分子水平上确诊一例性联高IgM综合征患儿
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  isotype switching
Mutations in the TNFR family member TACI (transmembrane activator and calcium-modulator and cyclophilin ligand interactor), which mediates isotype switching in B cells, were found to be present in 5% of patients with CVID.
      
B cells from individuals with TACI mutations did not produce IgG and IgA in response to the TACI ligand, APRIL (a proliferation-inducing ligand), probably reflecting impaired isotype switching.
      
Engagement of the B cell antigen CD40 by the CD40 ligand (CD40L) expressed on T cells leads to subsequent isotype switching during immunoglobulin synthesis in B cells.
      
The CD40-CD40L interaction is well established as a key signal for the induction of isotype switching while the elucidation of the role of other cell-cell interactions, for example, through adhesion molecules, needs further study.
      
It can skew T helper cell development, suppress T cell proliferation, stimulate cytotoxic T cell activity, induce isotype switching in B cells, and has diverse effects on innate immune cells.
      
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Objective To identify the inherited mode of sporadic hyper IgM syndrome (HIM) in a Chinese patient and to lay a foundation for the future gene therapy for the patients. Methods IgG, IgA, and IgM secretion by peripheral blood mononuclear cells in vitro was examined with enzyme linked immunosorbent assay. Ligand (CD 40 L) expression on activated T cells was detected by staining with CD 40 LmAb. Direct sequencing was used to identify the mutations on CD 40 L cDNA open reading frame. Results...

Objective To identify the inherited mode of sporadic hyper IgM syndrome (HIM) in a Chinese patient and to lay a foundation for the future gene therapy for the patients. Methods IgG, IgA, and IgM secretion by peripheral blood mononuclear cells in vitro was examined with enzyme linked immunosorbent assay. Ligand (CD 40 L) expression on activated T cells was detected by staining with CD 40 LmAb. Direct sequencing was used to identify the mutations on CD 40 L cDNA open reading frame. Results Costimulation of B cells in vitro from the sporadic HIM patient resulted in IgG production. CD 40 L expression was completely negative. Sequencing analysis showed a 4 base deletion (AGAT) at 654 657 in the patient′s CD 40 L open reading frame. Conclusion Failure of B cells to undergo immunoglobulin isotype switch in this case is a result of mutation on the CD 40 L gene in the activated T cells and B cells may have the ability to secrete IgG. This is the first case of HIGM with X linked inheritance diagnosed at a molecular level in China.

目的揭示1例散发型高IgM综合征(HIM)患儿发病机制及其遗传类型,从而为其今后可能的基因治疗打下基础。方法用夹心酶联免疫吸附试验(ELISA)法检测患儿外周血单个核细胞分泌免疫球蛋白的能力;用单克隆抗体染色检测CD40配体(CD40L)表达情况;聚合酶链反应(PCR)产物直接序列分析检测患儿CD40L开放阅读框架基因突变。结果此例HIM患儿B细胞体外刺激可产生IgG,T细胞表面CD40L染色阴性,序列分析发现654657位碱基缺失。结论患儿B细胞可能具有正常Ig分泌功能,Ig同种型转换障碍是由于其T细胞CD40L基因缺失,并在国内首次从分子水平上确诊一例性联高IgM综合征患儿

 
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