The Journal of Experimental Medicine
Rockland Immunochemicals for Research
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 7 August 2006 doi:10.1084/jem.20061067
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 203, Number 9, 2085-2094
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 2298K)
Right arrow PPT slides of all figures
Right arrow Supplemental Material Index
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Xue, K.
Right arrow Articles by Neuberger, M. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Xue, K.
Right arrow Articles by Neuberger, M. S.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

ARTICLE

 The in vivo pattern of AID targeting to immunoglobulin switch regions deduced from mutation spectra in msh2–/– ung–/– mice

Kanmin Xue, Cristina Rada, and Michael S. Neuberger

Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 2QH, UK

CORRESPONDENCE Michael Neuberger: msn{at}mrc-lmb.cam.ac.uk

Immunoglobulin (Ig) class switching is initiated by deamination of C->U within the immunoglobulin heavy chain locus, catalyzed by activation-induced deaminase (AID). In the absence of uracil-DNA glycosylase (UNG) and the homologue of bacterial MutS (MSH)–2 mismatch recognition protein, the resultant U:G lesions are not processed into switching events but are fixed by replication allowing sites of AID-catalyzed deamination to be identified by the resulting C->T mutations. We find that AID targets cytosines in both donor and acceptor switch regions (S regions) with the deamination domains initiating ~150 nucleotides 3' of the I exon start sites and extending over several kilobases (the IgH intronic enhancer is spared). Culturing B cells with interleukin 4 or interferon {gamma} specifically enhanced deamination around S{gamma}1 and S{gamma}2a, respectively. Mutation spectra suggest that, in the absence of UNG and MSH2, AID may occasionally act at the µ switch region in an apparently processive manner, but there is no marked preference for targeting of the transcribed versus nontranscribed strand (even in areas capable of R loop formation). The data are consistent with switch recombination being triggered by transcription-associated, strand-symmetric AID-mediated deamination at both donor and acceptor S regions with cytokines directing isotype specificity by potentiating AID recruitment to the relevant acceptor S region.

Abbreviations used: AID, activation-induced deaminase; MSH, homologue of bacterial MutS; S region, switch region; Sµ, µ switch region; UNG, uracil-DNA glycosylase.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS