CLONAL DIVERSITY AND T-CELL RECEPTOR BETA-CHAIN VARIABLE GENE-EXPRESSION IN ENLARGED LYMPH-NODES OF MRL-LPR-LPR LUPUS MICE
CLONAL DIVERSITY AND T-CELL RECEPTOR BETA-CHAIN VARIABLE GENE-EXPRESSION IN ENLARGED LYMPH-NODES OF MRL-LPR-LPR LUPUS MICE
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DOI：
10.1073/pnas.83.18.7018
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发表时间：
1986-09-01
影响因子：
11.1
通讯作者：
THEOFILOPOULOS, AN
中科院分区：
文献类型：
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作者：
SINGER, PA;MCEVILLY, RJ;THEOFILOPOULOS, AN
常染色体隐性lpr基因加速遗传易感小鼠的系统性狼疮样疾病，并在正常遗传背景的小鼠中诱导自身抗体。lpr基因的分子作用模式及其染色体位置仍不清楚，但它主要表现为大量T细胞增殖，仅在胸腺存在时才表现出来。为了确定在MRL-1 pr/1 pr小鼠的肿大淋巴结中发现的异常增殖T细胞的克隆多样性和成熟阶段，以及它们在自身反应性B细胞活化中的可能作用，我们分析了它们的T细胞受体β-受体。链可变区（V β）基因序列二十五个含VDJ的β-检查了10条链cDNA序列，发现每条序列都来源于正确阅读框中的不同重排，产生可翻译的β-链mRNA。另外10个克隆来源于截短的非功能性mRNA。D β 1和D β 2元件同样用于测序克隆中，并且可能的12个小鼠J β中的10个被测序克隆中的D β 1和D β 2元件被测序克隆中的10个。元素被代表。值得注意的是，60%的功能性β-链mRNA表达V β 8.2或V β 8.3基因，而同样同源的V β 8.1基因根本不存在。其他V β在文库中以较低的频率发现了基因，包括一个先前未鉴定的V β。基因结果表明，MRL-1 pr/1 pr小鼠中异常增殖淋巴结T细胞的克隆组成是异质的，但V β基因表达明显偏向V β 8.2/8.3基因。V β 8基因的优先表达可能是由lpr基因诱导的T细胞胸腺加工修饰引起的，并且与lpr基因相关的自身免疫有关。
The autosomal recessive lpr gene accelerates a systemic lupus erythematosus-like disease in genetically predisposed mice and induces autoantibodies in mice of normal genetic background. The molecular mode(s) of action of the lpr gene and its chromosomal location remain unknown, but it is primarily expressed as a massive T-cell proliferation manifested only in the presence of a thymus. To define the clonal diversity and maturational stage of the abnormally proliferation T cells found in enlarged lymph nodes of MRL-lpr/lpr mice, and their possible role in autoreactive B-cell activation, we analyzed their T-cell receptor .beta.-chain variable region (V.beta.) gene sequences. Twenty-five VDJ-containing .beta.-chain cDNA sequences were examined, each of which was found to derive from a distinct rearrangement in the correct reading frame, yielding translatable .beta.-chain mRNAs. An additional 10 clones were derived from truncated nonfunctional mRNAs. D.beta.1 and D.beta.2 elements were used equally in the sequenced clones, and 10 of the possible 12 mouse J.beta. elements were represented. Remarkably, 60% of the functional .beta.-chain mRNAs expressed V.beta.8.2 or V.beta.8.3 genes, whereas the equally homologous V.beta.8.1 gene was not represented at all. Other V.beta. genes were found at lower frequencies in the library, including one previously unidentified V.beta. gene. The results indicate that the clonal makeup of the abnormality proliferating lymph node T cells in MRL-lpr/lpr mice is heterogeneous, but V.beta. gene expression is significantly skewed in favor of V.beta.8.2/8.3 genes. The preferential representation of V.beta.8 genes might be caused by lpr gene-induced modification of T-cell thymic processing and relate to the lpr gene-associated autoimmunity.