Anti-insulin and regulatory anti-idiotypic antibodies use the same germ-line VHIX gene.
Anti-insulin and regulatory anti-idiotypic antibodies use the same germ-line VHIX gene.
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抗胰岛素和调节性抗独特型抗体使用相同的种系 VHIX 基因。
DOI：
10.1002/eji.1830220938
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发表时间：
1992
影响因子：
5.4
通讯作者：
Thomas,JW
中科院分区：
文献类型：
--
作者：
Thomas,JW
在人类和BALB/c小鼠中，对激素胰岛素的免疫应答使用进化相关的VHV（人类）和VHIX（小鼠）基因家族。为了确定这些结构关系是否包括调节元件，用识别人抗胰岛素抗体上共享独特表位的自体免疫球蛋白G（IgG）单克隆抗体（mAb）预处理BALB/c小鼠，并评估随后对人胰岛素的免疫应答。发现一种mAb Id 227通过诱导胰岛素结合和非胰岛素结合BALB/c抗体上表达的人独特型来增强和加速胰岛素应答。Id 227的VH基因利用分析表明，其表达与抗胰岛素mAb 125相似的VHIX基因，但抗Id无抗胰岛素活性。使用DNA扩增，从BALB/c肝脏DNA中分离出4个生殖系VHIX基因，序列分析显示抗胰岛素和抗Id来自相同的生殖系基因。与其作为调控独特型的作用一致，IgG Id 227完全保留了补体决定区中的种系序列，并且在框架区仅包含三个突变。这些研究表明，保守的自身抗原的免疫反应的结构和调节功能超出了物种的界限。
In humans and in BALB/c mice, immune responses to the hormone insulin use evolutionarily related VHV (human) and VHIX (murine) gene families. To determine if these structural relationships include regulatory elements, BALB/c mice were pretreated with autologous immunoglobulin G (IgG) monoclonal antibodies (mAb) that recognize shared idiotopes on human anti‐insulin antibodies and the subsequent immune response to human insulin assessed. One mAb, Id227, was found to augment and accelerate the insulin response by inducing a human idiotype that is expressed on both insulin‐binding and non‐insulin‐binding BALB/c antibodies. Analysis of VHgene utilization by Id227 shows that it expresses a VHIX gene similar to that of anti‐insulin mAb 125, but the anti‐Id has no anti‐insulin activity. Using DNA amplification, four germ‐line VHIX genes were isolated from BALB/c liver DNA and sequence analysis shows that the anti‐insulin and anti‐Id are derived from the same germ‐line gene. Consistent with its role as a regulatory idiotype, IgG Id227 entirely preserves germ‐line sequence in the complementray determining regions and contains only three mutations in framework regions. These studies show that both structural and regulatory features of immune responses to conserved self antigens extend beyond species boundaries.