Somatic hypermutation of immunoglobulin genes is a unique, targeted, adaptive process. While B cells are engaged in germinal centres in T-dependent responses, single base substitutions are introduced in the expressed V h/V l genes to allow the selection of mutants with a higher affinity for the immunizing antigen. Almost every possible DNA transaction has been proposed to explain this process, but each of these models includes an error-prone DNA synthesis step that introduces the mutations1,2. The Y family of DNA polymerases3—pol η, pol ι, pol κ and rev1—are specialized for copying DNA lesions and have high rates of error when copying a normal DNA template4,5. By performing gene inactivation in a Burkitt's lymphoma cell line inducible for hypermutation, we show here that somatic hypermutation is dependent on DNA polymerase iota.
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We thank B. Fleckenstein for the CB15 cell line; H. Mossafa for the cytogenetic analysis of pol-ι-null clones; R. Woodgate for pol-ι -specific reagents; M. Radman for critically editing the manuscript. This work was supported by the Fondation Princesse Grace de Monaco and the Ligue Nationale Française contre le Cancer (Equipe labellisée). A.F. and S.A. have been supported during part of this work by the Fondation de France (Fondation contre la Leucémie). C.-A.R. and J.-C.W. share senior authorship.
The authors declare that they have no competing financial interests.
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Faili, A., Aoufouchi, S., Flatter, E. et al. Induction of somatic hypermutation in immunoglobulin genes is dependent on DNA polymerase iota. Nature 419, 944–947 (2002). https://doi.org/10.1038/nature01117
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