Accelerated appearance of multiple B cell lymphoma types in NFS/N mice congenic for ecotropic murine leukemia viruses
Accelerated appearance of multiple B cell lymphoma types in NFS/N mice congenic for ecotropic murine leukemia viruses
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DOI：
10.1038/labinvest.3780020
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发表时间：
2000-02-01
影响因子：
5
通讯作者：
Fredrickson, TN
中科院分区：
文献类型：
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作者：
Hartley, JW;Chattopadhyay, SK;Fredrickson, TN
在NFS.V+小鼠中，自发性淋巴瘤的发生频率很高，这些小鼠是嗜亲性鼠白血病病毒（MuLV）前病毒基因的同基因品系，并高滴度表达病毒。在本研究中，通过组织病理学、免疫表型分析、免疫球蛋白重链或T细胞受体β链重排以及体细胞嗜亲性MuLV整合，对总共703例NFS.V+淋巴瘤进行了研究；90%受检的淋巴瘤为B细胞谱系。低度恶性肿瘤包括小淋巴细胞性、滤泡性和脾边缘区淋巴瘤，而高度恶性肿瘤包括弥漫性大细胞（中心母细胞型和免疫母细胞型）、脾边缘区和淋巴母细胞性淋巴瘤。对除了具有（NFS.V+）或不具有（NFS.V -）功能性嗜亲性MuLV基因组之外遗传背景相似的小鼠进行比较，结果表明NFS.V - 克隆性淋巴瘤的发生速率约为NFS.V+小鼠的一半，并且大多数是潜伏期较长的低度B细胞淋巴瘤。在NFS.V+小鼠中，由Ig基因重排所定义的克隆性增殖与体细胞嗜亲性前病毒整合的获得有关，这表明尽管B细胞克隆的产生可以不依赖病毒，但嗜亲性病毒可能会提高克隆产生的速率并加速其向淋巴瘤的演变。其机制仍不明确，因为在先前与MuLV插入诱变相关的几个细胞位点中仅检测到极少数重排。
Spontaneous lymphomas occur at high frequency in NFS.V+ mice, strains congenic for ecotropic murine leukemia virus (MuLV) proviral genes and expressing virus at high titer. In the present study, a total of 703 NFS.V+ lymphomas were studied by histopathology, immunophenotypic analysis, immunoglobulin heavy chain or T cell receptor beta chain rearrangements, and somatic ecotropic MuLV integrations; 90% of the lymphomas tested were of B cell lineage. Low-grade tumors included small lymphocytic, follicular, and splenic marginal zone lymphomas, while high-grade tumors comprised diffuse large-cell (centroblastic and immunoblastic types), splenic marginal zone, and lymphoblastic lymphomas. Comparison of mice of similar genetic background except for presence (NFS.V+) or absence (NFS.V-) of functional ecotropic MuLV genomes showed that NFS.V- clonal lymphomas developed at about one-half the rate of those occurring in NFS.V+ mice, and most were low-grade B cell lymphomas with extended latent periods. In NFS.V+ mice, clonal outgrowth, defined by Ig gene rearrangements, was associated with acquisition of somatic ecotropic proviral integrations, suggesting that, although generation of B cell clones can be virus independent, ecotropic virus may act to increase the rate of generation of clones and speed their evolution to lymphoma. The mechanism remains undefined, because only rare rearrangements were detected in several cellular loci previously associated with MuLV insertional mutagenesis.