Impaired up‐regulation of CD86 in B cells of "type A" common variable immunodeficiency patients
Impaired up‐regulation of CD86 in B cells of "type A" common variable immunodeficiency patients
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“A 型”常见变异型免疫缺陷患者 B 细胞中 CD86 上调受损
DOI：
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发表时间：
2000
影响因子：
5.4
通讯作者：
H. Peter
中科院分区：
文献类型：
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作者：
A. Denz;H. Eibel;H. Illges;Georg Kienzle;M. Schlesier;H. Peter
常见变异型免疫缺陷（CVID）的特征是B细胞成熟和抗体形成缺陷，导致大多数或所有IG同种型的血清抗体水平低。特定亚组患者（“A型”）具有正常数量的成熟表面IgM / sIgD阳性循环B细胞。然而，由于这些淋巴细胞不响应于通过分化和IG合成的体外刺激，它们似乎患有迄今未知的内在缺陷。通过分析大量B细胞活化特异性表面标志物的表达模式，我们发现，与健康供体和非A型CVID患者的B细胞相比，A型CVID患者的CD 28/ CTLA-4配体CD 86（B7 - 2）和淋巴细胞活化标志物CD w 137的表达高度降低。发现降低的CD 86表达水平与降低的CD 86 mRNA水平相关。由于通过B细胞抗原受体和CD 40交联的联合刺激不能挽救CD 86和CD w 137表达的缺陷，CVID A型患者的B细胞类似于不能与T细胞合作的功能无应答淋巴细胞。这些细胞在A型CVID患者中积累的事实表明与这种疾病的发病机制存在因果关系。
Common variable immunodeficiency (CVID) is characterized by defective B cell maturation and antibody formation resulting in low serum antibody levels of most or all Ig isotypes. A specific subgroup of patients ("type A") has normal numbers of mature surface (s)IgM / sIgD‐ positive circulating B cells. However, since these lymphocytes do not respond to in vitro stimulation by differentiation and Ig synthesis, they seem to suffer from so far unknown intrinsic defects. Analyzing the expression pattern of a large set of B cell activation‐specific surface markers, we found that type A CVID patients show a highly reduced expression of the CD28 / CTLA‐4 ligand CD86 (B7‐2) and of the lymphocyte activation marker CDw137 when compared to B cells of healthy donors and non‐type‐A CVID patients. The lowered CD86 expression levels were found to correlate with reduced levels of CD86 mRNA. Since combined stimulation via B cell antigen receptor and CD40 cross‐linking did not rescue the defects in CD86 and CDw137 expression, B cells of CVID type A patients resemble functionally unresponsive lymphocytes incapable of cooperating with T cells. The fact that these cells accumulate in type A CVID patients suggests a causal relationship with the pathogenesis of this disease.