AID-dependent somatic hypermutation occurs as a DNA single-strand event in the BL2 cell line

被引:147
作者
Faili, A
Aoufouchi, S
Guéranger, Q
Zober, C
Léon, A
Bertocci, B
Weill, JC
Reynaud, CA [1 ]
机构
[1] Fac Med Necker Enfants Malad, INSERM, U373, Paris, France
[2] EFS, Creteil, France
关键词
D O I
10.1038/ni826
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Immunoglobulin (Ig) gene hypermutation can be induced in the BL2 Burkitt's lymphoma cell line by IgM cross-linking and coculture with normal or transformed T helper clones. We describe here a T cell-independent in vitro induction assay, by which hypermutation is induced in BL2 cells through simultaneous aggregation of three surface receptors: IgM, CD19 and CD21. The mutations arise as a post-transcriptional event within 90 min. They are stably introduced in the G1 phase of the cell cycle, occurring in one of the two variable gene DNA strands, and eventually become fixed by replication in one of the daughter cells. Inactivation of AID (activation-induced cytidine deaminase) by homologous recombination in BL2 cells completely inhibits the process, thus validating this induction procedure as a model for the in vivo mechanism.
引用
收藏
页码:815 / 821
页数:7
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