Kosmas C, Stamatopoulos K, Papadaki T, Belessi C, Yataganas X, Anagnostou D, Loukopoulos D
First Department of Medicine, University of Athens School of Medicine, Laikon General Hospital, Greece.
Immunol Rev. 1998 Apr;162:281-92. doi: 10.1111/j.1600-065x.1998.tb01448.x.
Analysis of the rearranged immunoglobulin variable region gene hypermutation has provided important information concerning the clonal history and ontogenetic origin of various B-cell lymphoproliferative disorders. Under the selective pressure of antigen, mutational events in immunoglobulin genes will fine tune survival of B-cell clones bearing immunoglobulin with high affinity for antigen. Our studies aimed at analyzing neoplastic disorders originating from germinal and post-germinal center B-cells: follicular lymphoma and multiple myeloma, respectively. Despite the already acknowledged evidence for a selectable distribution of mutations within the clonal immunoglobulin variable heavy chain genes, very little is known about the contribution of light chains in the process of antigen selection. In follicular lymphoma, a more limited pattern of somatic mutation with less evidence of antigen selection was observed in variable kappa light chain genes (40%) than in their partner heavy chain genes (80%). In myeloma, hypermutation of variable light chain genes, with a distribution suggestive of antigen selection, was frequently observed. Based on these data and recent reports it appears that the light chain expressed by the clonogenic myeloma B-cells plays a pivotal role in the antigen selection process. Additionally, abortive kappa light chain variable region genes in lambda-expressing myelomas carried a significant number of somatic mutations indicating that the cell of origin is open to the hypermutation machinery at that particular developmental stage irrespective of antigen selection.
对重排的免疫球蛋白可变区基因超突变的分析，为各种B细胞淋巴增殖性疾病的克隆历史和个体发生起源提供了重要信息。在抗原的选择压力下，免疫球蛋白基因中的突变事件将微调那些带有对抗原有高亲和力免疫球蛋白的B细胞克隆的存活情况。我们的研究旨在分析分别起源于生发中心和生发中心后B细胞的肿瘤性疾病：滤泡性淋巴瘤和多发性骨髓瘤。尽管已有证据表明克隆性免疫球蛋白可变重链基因内的突变存在可选择的分布，但关于轻链在抗原选择过程中的作用却知之甚少。在滤泡性淋巴瘤中，与可变重链基因（80%）相比，可变κ轻链基因（40%）中观察到的体细胞突变模式更为有限，且抗原选择的证据较少。在骨髓瘤中，经常观察到可变轻链基因的超突变，其分布提示存在抗原选择。基于这些数据和近期报告，似乎克隆性骨髓瘤B细胞表达的轻链在抗原选择过程中起关键作用。此外，表达λ链的骨髓瘤中无效的κ轻链可变区基因携带大量体细胞突变，这表明起源细胞在那个特定发育阶段对超突变机制是开放的，而与抗原选择无关。
