Capello Daniela, Cerri Michaela, Muti Giuliana, Lucioni Marco, Oreste Pierluigi, Gloghini Annunziata, Berra Eva, Deambrogi Clara, Franceschetti Silvia, Rossi Davide, Alabiso Oscar, Morra Enrica, Rambaldi Alessandro, Carbone Antonino, Paulli Marco, Gaidano Gianluca
Department of Clinical and Experimental Medicine & IRCAD, Division of Hematology, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy.
Hematol Oncol. 2006 Dec;24(4):212-9. doi: 10.1002/hon.791.
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.
移植后淋巴细胞增生性疾病（PTLD）起源于经历过抗原刺激的B细胞，是实体器官移植的主要并发症。我们对50例PTLD（多形性PTLD，n = 10；弥漫性大B细胞淋巴瘤，n = 35；伯基特/伯基特样淋巴瘤，n = 5）中免疫球蛋白可变区（IGV）基因重排的使用情况、突变频率和突变模式进行了特征分析分析分析。在产生克隆性IGV扩增子的PTLD中，40/50（80.0%）例发现功能性IGV重链（IGHV）重排，而36/46（78.3%）例PTLD中鉴定出潜在功能性IGV轻链重排。通过联合IGHV和IGV轻链重排，10/50（20.0%）例PTLD携带严重突变，阻止功能性B细胞受体（BCR）的表达。免疫组织化学显示，仅18/43（41.9%）例PTLD中可检测到IG轻链表达。未能检测到与IGV表达缺失相关的功能性IGV重排。我们的数据表明，大部分PTLD起源于经历生发中心（GC）的B细胞，这些B细胞显示BCR受损。由于在GC迁移过程中正常B细胞存活需要功能性BCR，PTLD的发生可能意味着从凋亡中拯救以及未能通过GC反应的B细胞的扩增。IGV基因座失活的高频率似乎是PTLD在免疫缺陷相关淋巴细胞增生性疾病中的一个独特特征。
