疟原虫感染促进基因组不稳定和AID依赖的B细胞淋巴瘤。
Plasmodium Infection Promotes Genomic Instability and AID-Dependent B Cell Lymphoma.
作者信息
Robbiani Davide F, Deroubaix Stephanie, Feldhahn Niklas, Oliveira Thiago Y, Callen Elsa, Wang Qiao, Jankovic Mila, Silva Israel T, Rommel Philipp C, Bosque David, Eisenreich Tom, Nussenzweig André, Nussenzweig Michel C
机构信息
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
出版信息
Cell. 2015 Aug 13;162(4):727-37. doi: 10.1016/j.cell.2015.07.019.
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 which 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 in which 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. PAPERCLIP.
五十多年前，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B细胞癌，其特征是c-myc癌基因与Igh之间发生染色体易位。感染是否会促进B细胞淋巴瘤，如果是，通过何种机制，目前尚不清楚。为了研究寄生虫病与淋巴瘤发生之间的关系，我们使用查巴迪疟原虫（Pc）在小鼠中引发慢性疟疾感染。Pc诱导生发中心（GCs）长期扩张，生发中心是独特的区域，B细胞在其中经历快速克隆扩增并表达激活诱导的胞苷脱氨酶（AID），一种DNA突变酶。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生率，但它会改变淋巴瘤的发生，有利于依赖AID且显示染色体易位的成熟B细胞淋巴瘤。因此，疟疾感染通过在GC B细胞中引发持久的AID表达，有利于成熟B细胞癌。回形针。
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