Gene conversion in human rearranged immunoglobulin genes

Darlow, J.M. and Stott, D.I. (2006) Gene conversion in human rearranged immunoglobulin genes. Immunogenetics, 58(7), pp. 511-522. (doi: 10.1007/s00251-006-0113-6)




Over the past 20 years, many DNA sequences have been published suggesting that all or part of the V<sub>H</sub> segment of a rearranged immunoglobulin gene may be replaced in vivo. Two different mechanisms appear to be operating. One of these is very similar to primary V(D)J recombination, involving the RAG proteins acting upon recombination signal sequences, and this has recently been proven to occur. Other sequences, many of which show partial V<sub>H</sub> replacements with no addition of untemplated nucleotides at the V<sub>H</sub>–V<sub>H</sub> joint, have been proposed to occur by an unusual RAG-mediated recombination with the formation of hybrid (coding-to-signal) joints. These appear to occur in cells already undergoing somatic hypermutation in which, some authors are convinced, RAG genes are silenced. We recently proposed that the latter type of V<sub>H</sub> replacement might occur by homologous recombination initiated by the activity of AID (activation-induced cytidine deaminase), which is essential for somatic hypermutation and gene conversion. The latter has been observed in other species, but not in human Ig genes, so far. In this paper, we present a new analysis of sequences published as examples of the second type of rearrangement. This not only shows that AID recognition motifs occur in recombination regions but also that some sequences show replacement of central sections by a sequence from another gene, similar to gene conversion in the immunoglobulin genes of other species. These observations support the proposal that this type of rearrangement is likely to be AID-mediated rather than RAG-mediated and is consistent with gene conversion.

Item Type:Articles
Keywords:Gene conversion, genes, immunoglobulin, humans, antibody diversity.
Glasgow Author(s) Enlighten ID:Stott I, Professor David
Authors: Darlow, J.M., and Stott, D.I.
Subjects:Q Science > QR Microbiology > QR180 Immunology
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Immunogenetics
Published Online:17 May 2006
Copyright Holders:Copyright © 2006 Springer
First Published:First published in Immunogenetics 58(7):511-522
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher.

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