Plasmodium Infection Promotes Genomic Instability and AID-Dependent B Cell Lymphoma.
Plasmodium Infection Promotes Genomic Instability and AID-Dependent B Cell Lymphoma.
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DOI：
10.1016/j.cell.2015.07.019
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发表时间：
2015-08-13
期刊：
影响因子：
64.5
通讯作者：
Nussenzweig MC
中科院分区：
文献类型：
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作者：
Robbiani DF;Deroubaix S;Feldhahn N;Oliveira TY;Callen E;Wang Q;Jankovic M;Silva IT;Rommel PC;Bosque D;Eisenreich T;Nussenzweig A;Nussenzweig MC
恶性疟原虫的慢性感染在流行病学上与地方性伯基特淋巴瘤相关，伯基特淋巴瘤是一种成熟的B细胞癌，50多年前以c-myc癌基因和Igh之间的染色体易位为特征。感染是否会促进B细胞淋巴瘤，如果是，通过什么机制促进B细胞淋巴瘤仍是未知的。为了探讨寄生虫病与淋巴瘤发生的关系，我们利用chabaudi疟原虫（Pc）在小鼠体内引起慢性疟疾感染。Pc诱导生发中心（GCs）的延长扩增，生发中心是B细胞进行快速克隆扩增和表达激活诱导胞苷脱氨酶（AID）的独特区室，这是一种DNA突变。在Pc感染期间引发的GC B细胞遭受广泛的DNA损伤，导致染色体易位。虽然感染不会改变总体发病率，但它改变了淋巴瘤的形成，使其倾向于依赖于AID并表现出染色体易位的成熟B细胞淋巴瘤。因此，疟疾感染通过在GC B细胞中诱导AID的长期表达而有利于成熟B细胞癌。
Chronic infection with Plasmodium falciparum was epidemiologically associated with endemic Burkitt’s lymphoma, a mature B cell cancer characterized by chromosome translocation between the c-myc oncogene and Igh, over 50 years ago. Whether infection promotes B cell lymphoma, and if so by what mechanism remains unknown. To investigate the relationship between parasitic disease and lymphomagenesis we used Plasmodium chabaudi (Pc) to produce chronic malaria infection in mice. Pc induces prolonged expansion of germinal centers (GCs), unique compartments where B cells undergo rapid clonal expansion and express activation-induced cytidine deaminase (AID), a DNA mutator. GC B cells elicited during Pc infection suffer widespread DNA damage leading to chromosome translocations. Although infection does not change the overall rate, it modifies lymphomagenesis to favor mature B cell lymphomas that are AID dependent and show chromosome translocations. Thus, malaria infection favors mature B cell cancers by eliciting protracted AID expression in GC B cells.