Over 30% of patients with splenic marginal zone lymphoma express the same immunoglobulin heavy variable gene: ontogenetic implications
Over 30% of patients with splenic marginal zone lymphoma express the same immunoglobulin heavy variable gene: ontogenetic implications
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DOI：
10.1038/leu.2012.3
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发表时间：
2012-07-01
期刊：
影响因子：
11.4
通讯作者：
Stamatopoulos, K.
中科院分区：
文献类型：
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作者：
Bikos, V.;Darzentas, N.;Stamatopoulos, K.
我们对 337 例边缘区原发性脾小 B 细胞淋巴瘤病例中的 345 个 IGHV-IGHD-IGHJ 重排进行了免疫遗传学分析。三种免疫球蛋白（IG）重变异（IGHV）基因占病例的45.8%（IGHV1-2，24.9%；IGHV4-34，12.8%；IGHV3-23，8.1%）。特别是对于 IGHV1-2 基因，不同等位基因的利用存在明显的强烈偏差，使用等位基因 *04 进行了 79/86 重排 (92%)。由于脾脏组织病理学标本的可用性，在更严格地分类为脾边缘区淋巴瘤 (SMZL) 的病例中，IGHV1-2*04 的频率最高为 31%。与所有其他情况相比，IGHV1-2*04 重排携带明显更长的互补决定区 3 (CDR3)，并显示出 IGHD 基因使用的偏差，导致 CDR3 具有共同基序。绝大多数分析的重排（299/345，86.7%）携带 IGHV 基因，并受到体细胞超突变的一些影响，从最小到显着。值得注意的是，75/79 (95%) IGHV1-2*04 重排发生了突变；然而，它们大多数（56/75 例；74.6%）携带少量突变（97-99.9% 种系同一性），具有保守性和有限的分布。 IG 受体的这些独特特征表明 SMZL 发病机制中（超）抗原元件的选择。此外，他们提出了一种可能性，即某些 SMZL 亚型可能源自通过选择 VH 结构域特异性（特别是 IGHV1-2*04 等位基因）适应特定抗原挑战的祖细胞群。
We performed an immunogenetic analysis of 345 IGHV-IGHD-IGHJ rearrangements from 337 cases with primary splenic small B-cell lymphomas of marginal-zone origin. Three immunoglobulin (IG) heavy variable (IGHV) genes accounted for 45.8% of the cases (IGHV1-2, 24.9%; IGHV4-34, 12.8%; IGHV3-23, 8.1%). Particularly for the IGHV1-2 gene, strong biases were evident regarding utilization of different alleles, with 79/86 rearrangements (92%) using allele *04. Among cases more stringently classified as splenic marginal-zone lymphoma (SMZL) thanks to the availability of splenic histopathological specimens, the frequency of IGHV1-2*04 peaked at 31%. The IGHV1-2*04 rearrangements carried significantly longer complementarity-determining region-3 (CDR3) than all other cases and showed biased IGHD gene usage, leading to CDR3s with common motifs. The great majority of analyzed rearrangements (299/345, 86.7%) carried IGHV genes with some impact of somatic hypermutation, from minimal to pronounced. Noticeably, 75/79 (95%) IGHV1-2*04 rearrangements were mutated; however, they mostly (56/75 cases; 74.6%) carried few mutations (97-99.9% germline identity) of conservative nature and restricted distribution. These distinctive features of the IG receptors indicate selection by (super) antigenic element(s) in the pathogenesis of SMZL. Furthermore, they raise the possibility that certain SMZL subtypes could derive from progenitor populations adapted to particular antigenic challenges through selection of VH domain specificities, in particular the IGHV1-2*04 allele.