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Induction of somatic hypermutation in immunoglobulin genes is dependent on DNA polymerase iota

Nature volume 419, pages 944–947 (2002)Cite this article

Abstract

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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Figure 1: Inactivation of the gene encoding pol ι in the BL2 cell line and restoration of protein expression by transfection with pol-ι cDNA.
Figure 2: No increase in pol-ι and AID protein is observed during induction of SHM.

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Acknowledgements

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.

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Author notes

  1. Ahmad Faili, Said Aoufouchi and Eric Flatter: These authors contributed equally to this work

  2. Jean-Claude Weill: Correspondence and requests for materials should be addressed to J.C.W.

Authors and Affiliations

  1. INSERM U373, Faculté de Médecine Necker-Enfants Malades, 156 rue de Vaugirard, 75730, Cedex, 15, Paris, France

    Ahmad Faili, Said Aoufouchi, Eric Flatter, Quentin Guéranger, Claude-Agnès Reynaud & Jean-Claude Weill

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  1. Ahmad Faili
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Correspondence to Jean-Claude Weill.

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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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