Activated B cells from patients with common variable immunodeficiency proliferate and synthesize immunoglobulin.
Activated B cells from patients with common variable immunodeficiency proliferate and synthesize immunoglobulin.
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来自常见变异型免疫缺陷患者的活化 B 细胞会增殖并合成免疫球蛋白。
DOI：
10.1172/jci116701
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Ochs,HD
中科院分区：
文献类型：
--
作者：
Nonoyama,S;Farrington,M;Ishida,H;Howard,M;Ochs,HD
大多数常见变异型免疫缺陷（CVI）患者循环B细胞数量正常，但血清IG浓度低。为了确定低丙种球蛋白血症是否由内在B细胞缺陷引起，我们研究了22例CVI患者的B细胞功能。所有CVI患者的培养B细胞在抗CD 40和IL-4存在下进行正常增殖并合成正常量的IgE。如果与抗-CD 40和IL-10一起培养，观察到四种IG同种型合成模式。6例CVI患者产生正常量的IgM、IgG和伊加。4例患者产生正常量的IgM和IgG。其余12例IgG和伊加合成失败的患者中，8例正常，4例IgM合成量减少。对10例IgG分泌型B细胞患者产生的IgG亚类进行分析，发现IgG 4是受影响最大的亚类，其次是IgG 2; IgG 3和IgG 1的合成保持正常。同样，在6名伊加产生患者中，IgA 2比IgA 1更常受到影响。IG同种型和亚类合成的层级对应于染色体14上的IG重链恒定区基因位置。因此，CVI患者的循环B细胞致力于合成一种或多种IG同种型或亚类，并且在适当的条件下可以增殖、成熟为Ig分泌细胞并经历向IgE的类别转换。
Most patients with common variable immunodeficiency (CVI) have normal numbers of circulating B cells but low concentrations of serum Ig. To determine if the hypogammaglobulinemia is caused by an intrinsic B cell defect, we studied B cell function of 22 CVI patients. Cultured B cells from all CVI patients underwent normal proliferation and synthesized normal quantities of IgE in the presence of anti-CD40 and IL-4. If cultured with anti-CD40 and IL-10, four patterns of Ig isotype synthesis were observed. Six CVI patients produced normal amounts of IgM, IgG, and IgA. Four patients produced normal quantities of IgM and IgG. Of the remaining 12 patients who failed to synthesize IgG and IgA, 8 produced normal and 4 synthesized decreased amounts of IgM. Analysis of the IgG subclasses produced by 10 patients with IgG-secreting B cells revealed that IgG4 was the most affected subclass, followed by IgG2; synthesis of IgG3 and IgG1 remained normal. Similarly, in the six IgA producing patients, IgA2 was more often affected than IgA1. The hierarchy of Ig isotype and subclass synthesis corresponds to Ig heavy chain constant region gene location on chromosome 14. Thus, circulating B cells of CVI patients are committed to synthesize one or more Ig isotypes or subclasses, and under proper conditions can proliferate, mature into Ig-secreting cells, and undergo class switch to IgE.