The Journal of Experimental Medicine
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Published 6 May 2002. doi:10.1084/jem.20011749
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© Rockefeller University Press, 0022-1007/2002/5/1187/ $5.00
The Journal of Experimental Medicine, Volume 195, Number 9, May 6, 2002 1187-1192

Brief Definitive Report

 DNA Double-Strand Breaks : Prior to but not Sufficient in Targeting Hypermutation



Linda Bross1,3, Masamichi Muramatsu2, Kazuo Kinoshita2, Tasuku Honjo2 and Heinz Jacobs1,3

1 Basel Institute for Immunology, CH-4005 Basel, Switzerland
2 Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan
3 Department of Immunology, Research Institute Growth and Development, University of Maastricht, NL-6200 MD Maastricht, Netherlands

Address correspondence to Heinz Jacobs, University of Maastricht, Research Institute Growth & Development, Dept. of Immunology, Universiteits Singel 50, 6200 MD Maastricht, The Netherlands. Phone: 31-43-388-2114; Fax: 31-43-388-4164; E-mail: h.jacobs{at}immuno.unimaas.nl

The activation-induced cytidine deaminase (AID) is required for somatic hypermutation (SHM) and class-switch recombination (CSR) of immunoglobulin (Ig) genes, both of which are associated with DNA double-strand breaks (DSBs). As AID is capable of deaminating deoxy-cytidine (dC) to deoxy-uracil (dU), it might induce nicks (single strand DNA breaks) and also DNA DSBs via a U-DNA glycosylase-mediated base excision repair pathway (‘DNA-substrate model’). Alternatively, AID functions like its closest homologue Apobec1 as a catalytic subunit of a RNA editing holoenzyme (‘RNA-substrate model’). Although rearranged V{lambda} genes are preferred targets of SHM we found that germinal center (GC) B cells of AID-proficient and -deficient V{lambda}1-expressing GC B cells display a similar frequency, distribution, and sequence preference of DSBs in rearranged and also in germline V{lambda}1 genes. The possible roles of DSBs in relation to AID function and SHM are discussed.

Key Words: AID • class-switch recombination • DSB • Ig{lambda} • somatic hypermutation


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