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伴发副肿瘤性天疱疮的Castleman瘤B细胞免疫球蛋白基因重排与超变分析 被引量:4

Immunoglobulin variable region gene rearrangement and hypermutation in paraneoplastic pemphigus associated Castleman’s tumor
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摘要 目的 :我科近来研究了副肿瘤性天疱疮 (PNP)患者肿瘤在发病中的作用 ,证明 1例Castleman瘤产生针对表皮连接蛋白的抗体。本文进一步探讨肿瘤和抗体在疾病发生过程中的作用和PNP的发病机制。方法 :对 1例副肿瘤性天疱疮伴发已经证明可分泌自身反应性抗体的Castleman瘤患者肿瘤B细胞进行培养 ,免疫组化分析其表面标志 ;扩增患者肿瘤组织的RNA ,将PCR产物克隆、测序。对B细胞克隆的免疫球蛋白可变区基因重排和超变区突变特点进行分析。结果 :培养肿瘤细胞多数为CD2 0、HLA DR、smIgM、smIgG阳性。克隆得到IgVH 与IGHV3 9 0 1胚系基因片段接近 ,IgVL与IGKV4 1 0 1胚系基因片段同源。VH和VL 基因CDRs区的核苷酸改变均明显多于FRs区 ,并且在VH和VL 基因观察到的CDRs区替换突变数目远大于可能发生随机突变的值。结论 :本例伴发Castleman瘤的副肿瘤性天疱疮患者的肿瘤中存在特殊B细胞克隆 ,其已重排的免疫球蛋白可变区基因CDRs超变区发生明显体细胞突变 ,可能是抗原选择的结果。该克隆经过免疫球蛋白类别转换 ,可能直接产生与表皮自身抗原特异性结合的自身反应性IgG。 Objective: We have studied the role of lymphoproliferative tumors in the pathogenesis of autoimmune and the origin of the autoantibodies in paraneoplastic pemphigus (PNP) in recent years. A Castleman’s tumor from a patient was identified to produce autoantibody. To identify the relationship between the tumor and pathogenesis of the disease, we analyzed the rearrangement of immunoglobulin variable region gene and its hypermutation in B cells of Castleman’s tumor from a patient who was diagnosed of paraneoplastic pemphigus. Methods: The surface-markers of cultured tumor lymphocytes were assessed with immunochemistry staining. After total RNA of the tumor cells were isolated, the mRNA was reversely transcribed into cDNA. V H and V L genes were cloned and their sequences were analyzed. Results: Immunochemistry staining and flow cytometer analysis showed that the tumor cells were CD20, HLA-DR, smIgM, and smIgG positive. The cloned IgV H and IGHV3-9*01 germ-line gene are homologous and so are the Ig V L and the IGKV4-1*01 germ-line gene. More nucleotide changes in the V H or V L occurred in CDRs than those in FRs. Conclusion: In this reported case, a clone of specific B-lymphocyte in the Castleman’s tumor carrying functional rearranged immunoglobulin heavy and light chain genes was found to have experienced switch recombination and was possible to produce IgG autoantibody.
出处 《北京大学学报(医学版)》 CAS CSCD 北大核心 2004年第5期454-461,共8页 Journal of Peking University:Health Sciences
基金 国家自然科学基金 ( 3 0 3 712 92 ) 2 0 0 3年度高等学校博士学科点专项科研基金 ( 2 0 0 3 0 0 0 10 2 1)资助~~
关键词 副肿瘤性天疱疮 B细胞 患者 免疫球蛋白 抗体 克隆 可变区基因 VL基因 PCR产物 随机突变 Pemphigus/etiol Giant lymph node hyperplasia Gene rearrangement,B-lymphocyte Mutation
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