Zhu Delin, Qi Chen Feng, Morse Herbert C, Janz Siegfried, Stevenson Freda K
Molecular Immunology Group, Tenovus Laboratory, Southampton University Hospitals Trust, Southampton SO16 6YD, United Kingdom.
Blood. 2005 Mar 1;105(5):2135-7. doi: 10.1182/blood-2004-07-2573. Epub 2004 Nov 2.
Chromosomal translocations juxtaposing immunoglobulin (Ig) and MYC genes are the hallmarks of human Burkitt lymphoma (BL), with deregulated MYC expression being a critical factor in pathogenesis. By inserting an intact mouse Myc gene into the mouse genome, proximal to the Ig enhancer Emu, the effect of a precise mimic of the major t(8;14) translocation of human endemic BL (eBL) could be investigated. Knock-in mice developed IgM-positive B-cell tumors, with most being typical of eBL by histology and immunophenotype, including expression of the germinal center (GC)-associated protein, BCL6. Unlike eBL, however, analysis of Ig V(H) sequences revealed no significant level of somatic mutation. Thus, constitutive expression of Myc in the knock-in mice is apparently able to induce "Burkitt-like" lymphomas before antigen stimulation and formation of a GC. In contrast, human eBL development occurs in a GC or post-GC site with a likely contribution to pathogenesis from Epstein-Barr virus (EBV) and other epigenetic factors.
免疫球蛋白（Ig）基因与MYC基因并列的染色体易位是人类伯基特淋巴瘤（BL）的标志，MYC表达失调是发病机制中的关键因素。通过将完整的小鼠Myc基因插入小鼠基因组中靠近Ig增强子Emu的位置，可以研究精确模拟人类地方性BL（eBL）主要t(8;14)易位的效果。敲入小鼠发生了IgM阳性B细胞肿瘤，大多数在组织学和免疫表型上具有eBL的典型特征，包括生发中心（GC）相关蛋白BCL6的表达。然而，与eBL不同的是，对Ig V(H)序列的分析显示没有明显水平的体细胞突变。因此，敲入小鼠中Myc的组成型表达显然能够在抗原刺激和GC形成之前诱导“伯基特样”淋巴瘤。相比之下，人类eBL的发生发生在GC或GC后位点，爱泼斯坦-巴尔病毒（EBV）和其他表观遗传因素可能对发病机制有贡献。
