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Activation-induced cytidine deaminase initiates immunoglobulin gene conversion and hypermutation by a common intermediate.

ABSTRACT: Depending on the species and the lymphoid organ, activation-induced cytidine deaminase (AID) expression triggers diversification of the rearranged immunoglobulin (Ig) genes by pseudo V (psiV) gene- templated gene conversion or somatic hypermutation. To investigate how AID can alternatively induce recombination or hypermutation, psiV gene deletions were introduced into the rearranged light chain locus of the DT40 B-cell line. We show that the stepwise removal of the psiV donors not only reduces and eventually abolishes Ig gene conversion, but also activates AID-dependent Ig hypermutation. This strongly supports a model in which AID induces a common modification in the rearranged V(D)J segment, leading to a conversion tract in the presence of nearby donor sequences and to a point mutation in their absence.

SUBMITTER: Arakawa H

PROVIDER: S-EPMC449846 | biostudies-literature | 2004 Jul

REPOSITORIES: biostudies-literature

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Activation-induced cytidine deaminase initiates immunoglobulin gene conversion and hypermutation by a common intermediate.

Arakawa Hiroshi H Saribasak Huseyin H Buerstedde Jean-Marie JM

PLoS biology 20040713 7

Depending on the species and the lymphoid organ, activation-induced cytidine deaminase (AID) expression triggers diversification of the rearranged immunoglobulin (Ig) genes by pseudo V (psiV) gene- templated gene conversion or somatic hypermutation. To investigate how AID can alternatively induce recombination or hypermutation, psiV gene deletions were introduced into the rearranged light chain locus of the DT40 B-cell line. We show that the stepwise removal of the psiV donors not only reduces a ...[more]

PMID: 15252444

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