Immunogenetic analysis of gastric MALT lymphoma-like lesions induced by Helicobacter pylori infection in neonatally thymectomized mice
Immunogenetic analysis of gastric MALT lymphoma-like lesions induced by Helicobacter pylori infection in neonatally thymectomized mice
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DOI：
10.1038/labinvest.3700056
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发表时间：
2004-04-01
影响因子：
5
通讯作者：
Chiba, T
中科院分区：
文献类型：
--
作者：
Fukui, T;Okazaki, K;Chiba, T
大多数胃粘膜相关淋巴组织（MALT）淋巴瘤是由幽门螺杆菌（H。pylori）感染。我们以前报道过H.幽门螺杆菌感染的小鼠胸腺切除（nTx）。在本研究中，我们通过长期H. pylori感染，并进行免疫遗传学分析。BALB/c小鼠出生后第3天切除胸腺。在6周龄时，小鼠经口感染108 H。pylori感染，并在2、4、6和12个月后连续处死。正常BALB/c和未感染的nTx小鼠作为对照。卵泡形成发生在H. pylori感染。卵泡形成和上皮内淋巴细胞浸润的进展呈时间依赖性。MALT淋巴瘤的一个特征性特征--上皮细胞病变也以时间依赖性方式发生（12个月时为100%）。感染后6个月，血清免疫电泳显示30%（3/10）的小鼠出现单克隆带（M蛋白）。用聚合酶链反应测定，M蛋白阳性小鼠胃B淋巴细胞中有一个或两个IgM和/或IgG重链基因扩增，表明单克隆或寡克隆性。12个月时80%（8/10）的病例Bcl-X-L蛋白在浸润的B淋巴细胞和部分滤泡B淋巴细胞中过表达。因此，H. pylori感染参与nTx小鼠胃MALT淋巴瘤样病变的发展。本模型为阐明H.幽门感染
Most gastric mucosa-associated lymphoid tissue (MALT) lymphomas are caused by Helicobacter pylori (H. pylori) infection. We previously reported that acquired lymphoid follicles with germinal centers were induced by H. pylori infection in neonatally thymectomized (nTx) mice. In the present study, we developed gastric MALT lymphoma-like lesions in nTx mice by long-term H. pylori infection, and performed immunogenetic analyses. BALB/c mice were thymectomized on the 3rd day after birth. At 6 weeks of age, mice were orally infected with 108 H. pylori and serially killed 2, 4, 6, and 12 months later. Normal BALB/c and noninfected nTx mice served as controls. Follicle formation occurred after 2 months of H. pylori infection in the nTx mice. Follicle formation and infiltration of intraepithelial lymphocytes progressed in a time-dependent manner. Lymphoepithelial lesions, a characteristic feature of MALT lymphoma, also occurred in a time-dependent manner (100% at 12 months). Serum immunoelectrophoresis revealed a monoclonal band (M-protein) in 30% (3/10) of mice 6 months after infection. M-protein-positive mice had amplification of one or two IgM and/or IgG heavy-chain genes in the gastric B lymphocytes, as determined with polymerase chain reaction, suggesting mono- or oligoclonality. Overexpression Of Bcl-X-L protein was immunohistologically observed in the infiltrating B lymphocytes and in some follicular B lymphocytes in 80% (8/10) of the cases at 12 months. Thus, H. pylori infection is involved in the development of gastric MALT lymphoma-like lesions in nTx mice. Our mouse model is useful for clarifying the pathogenetic mechanism of gastric MALT lymphoma by H. pylori infection.