AID-dependent somatic hypermutation occurs as a DNA single-strand event in the BL2 cell line.
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#150;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.
Faili
Ahmad
A
INSERM U373, Faculté de Médecine Necker-Enfants Malades, Paris, France.
Aoufouchi
Said
S
Guéranger
Quentin
Q
Zober
Carole
C
Léon
Anne
A
Bertocci
Barbara
B
Weill
Jean-Claude
JC
Reynaud
Claude-Agnès
CA
D002051:Burkitt Lymphoma / Q000276:immunology; D003564:Cytidine Deaminase / Q000502:physiology*; D004249:DNA Damage; D004277:DNA, Single-Stranded / Q000235:genetics*; D016193:G1 Phase; D006801:Humans; D012333:RNA, Messenger / Q000096:biosynthesis; D011995:Recombination, Genetic; D027041:Somatic Hypermutation, Immunoglobulin; D013601:T-Lymphocytes / Q000502:physiology; D014407:Tumor Cells, Cultured; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D004277:DNA, Single-Stranded; D012333:RNA, Messenger; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase