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lüll Mechanism of antigen-driven somatic hypermutation of rearranged immunoglobulin V(D)J genes in the mouse Steele EJ; Rothenfluh HS; Blanden RVImmunol Cell Biol 1997[Feb]; 75 (1): 82-95Available data relevant to the mechanism of somatic hypermutation have been critically evaluated in the context of alternative models: (i) error-generating reverse transcription (RT) followed by homologous recombination; and (ii) error-prone DNA replication/repair. A set of basic principles concerning somatic hypermutation has also been formulated and a revised and expanded "RT-Mutatorsome" concept (analogous to telomerase) is presented which is consistent with these principles and all data on the distribution of somatic mutations in normal and Ig transgenic mice carrying particular V(D)J and flanking region constructs. It is predicted that in the mouse VH and Vk loci. the J-C intronic Enhancer-Nuclear Matrix Attachment Region (Ei/MAR) contains a unique sequence motif or secondary structure which ensures that only V(D)J sequences mutate whilst other regions of the genome are not mutated.|Animals[MESH]|Antigens/*immunology/physiology[MESH]|Gene Rearrangement/immunology/physiology[MESH]|Genes, Immunoglobulin/*genetics/physiology[MESH]|Immunoglobulin Heavy Chains/genetics/immunology[MESH]|Mice[MESH]|Mutation/genetics/*immunology/physiology[MESH] |