CLONAL EVOLUTION OF A FOLLICULAR LYMPHOMA - EVIDENCE FOR ANTIGEN SELECTION
CLONAL EVOLUTION OF A FOLLICULAR LYMPHOMA - EVIDENCE FOR ANTIGEN SELECTION
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DOI：
10.1073/pnas.89.15.6770
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发表时间：
1992-08-01
影响因子：
11.1
通讯作者：
LEVY, R
中科院分区：
文献类型：
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作者：
BAHLER, DW;LEVY, R
抗原在滤泡性淋巴瘤的生长刺激或克隆选择中的潜在作用尚不清楚。为了研究这个问题，我们测序的免疫球蛋白重链可变区基因表达的滤泡性淋巴瘤从多个活检标本，也克隆和测序相应的生殖系可变基因从这个病人。与生殖系基因的比较揭示了所有淋巴瘤可变基因序列中的许多核苷酸替换。一些替换可能发生在引起这种淋巴瘤的非恶性前体B细胞中，因为它们在所有可变基因中共享，但许多突变随着恶性克隆的扩增而积累。这些突变的分布方式强烈表明，大多数肿瘤细胞是通过其抗原受体被阳性选择的。这是特别明显的突变，发展后期的克隆进化的淋巴瘤。这些发现表明抗原刺激可能参与滤泡性淋巴瘤肿瘤的生长。
The potential role antigens play in growth stimulation or in clonal selection of follicular lymphomas is unknown. To study this issue, we sequenced the immunoglobulin heavy chain variable region genes expressed by a follicular lymphoma from multiple biopsy specimens and also cloned and sequenced the corresponding germ-line variable gene from this patient. Comparison to the germ-line gene revealed numerous nucleotide substitutions in all of the lymphoma variable gene sequences. Some of the substitutions may have occurred in the nonmalignant precursor B cell that gave rise to this lymphoma because they were shared among all of the variable genes, but many of the mutations accumulated as the malignant clone expanded. The mutations were distributed in such a way that strongly suggested the majority of tumor cells had been positively selected through their antigen receptor. This was especially evident for the mutations that developed late in the clonal evolution of this lymphoma. These findings indicate that antigen stimulation may be involved in the growth of follicular lymphoma tumors.