Analysis of immunoglobulin heavy and light chain variable genes in post-transplant lymphoproliferative disorders
Analysis of immunoglobulin heavy and light chain variable genes in post-transplant lymphoproliferative disorders
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DOI：
10.1002/hon.791
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发表时间：
2006-12-01
影响因子：
3.3
通讯作者：
Gaidano, Gianluca
中科院分区：
文献类型：
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作者：
Capello, Daniela;Cerri, Michaela;Gaidano, Gianluca
移植后淋巴组织增生性疾病（PTLD）来源于抗原经历的B细胞，是实体器官移植的主要并发症。我们在50例PTLD（多态性PTLD，n = 10;弥漫性大B细胞淋巴瘤，n = 35; Burkitt/Burkitt样淋巴瘤，n = 5）中描述了免疫球蛋白可变区（IGV）基因重排的使用、突变频率和突变模式。在产生克隆IGV扩增物的PTLD中，在40/50（80.0%）例病例中发现功能性IGV重链（IGHV）重排，而在36/46（78.3%）PTLD中鉴定出潜在功能性IGV轻链重排。通过结合IGHV和IGV轻链重排，10/50（20.0%）PTLD携带致残突变，排除功能性B细胞受体（BCR）的表达。免疫组化结果显示，只有18/43例（41.9%）PTLD中可检测到IG轻链的表达。未能检测到与IGV表达缺乏相关的功能性IGV重排。我们的数据表明，PTLD的大部分产生于生发中心（GC）经历的B细胞，显示受损的BCR。由于功能性BCR是GC转运过程中正常B细胞存活所必需的，PTLD的发展可能涉及对GC反应失败的B细胞凋亡和扩增的拯救。IGV基因座失活的高频率似乎是PTLD的免疫缺陷相关的淋巴细胞增生的一个独特的功能。版权所有（c）2006约翰威利父子有限公司。
Post-transplant lymphoproliferative disorders (PTLD) derive from antigen-experienced B-cells and represent a major complication of solid organ transplantation. We characterized usage, mutation frequency and mutation pattern of immunoglobulin variable (IGV) gene rearrangements in 50 PTLD (polymorphic PTLD, n = 10; diffuse large B-cell lymphoma, n = 35; and Burkitt/Burkitt-like lymphoma, n = 5). Among PTLD yielding clonal IGV amplimers, a functional IGV heavy chain (IGHV) rearrangement was found in 40/50 (80.0%) cases, whereas a potentially functional IGV light chain rearrangement was identified in 36/46 (78.3%) PTLD. By combining IGHV and IGV light chain rearrangements, 10/50 (20.0%) PTLD carried crippling mutations, precluding expression of a functional B-cell receptor (BCR). Immunohistochemistry showed detectable expression of IG light chains in only 18/43 (41.9%) PTLD. Failure to detect a functional IGV rearrangement associated with lack of IGV expression. Our data suggest that a large fraction of PTLD arise from germinal centre (GC)-experienced B-cells that display impaired BCR. Since a functional BCR is required for normal B-cell survival during GC transit, PTLD development may implicate rescue from apoptosis and expansion of B-cells that have failed the GC reaction. The high frequency of IGV loci inactivation appears to be a peculiar feature of PTLD among immunodeficiency-associated lymphoproliferations. Copyright (c) 2006 John Wiley & Sons, Ltd.