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Immunology. 2014 Feb;141(2):268-75. doi: 10.1111/imm.12192.

Characterization of a new V gene replacement in the absence of activation-induced cytidine deaminase and its contribution to human B-cell receptor diversity.

Author information

1
Unité EA4666, SFR CAP Santé, Université Picardie Jules Verne, Amiens, France; Unité Inserm U925, Université Picardie Jules Verne, Amiens, France.

Abstract

In B cells, B-cell receptor (BCR) immunoglobulin revision is a common route for modifying unwanted antibody specificities via a mechanism called VH replacement. This in vivo process, mostly affecting heavy-chain rearrangement, involves the replacement of all or part of a previously rearranged IGHV gene with another germline IGHV gene located upstream. Two different mechanisms of IGHV replacement have been reported: type 1, involving the recombination activating genes complex and requiring a framework region 3 internal recombination signal; and type 2, involving an unidentified mechanism different from that of type 1. In the case of light-chain loci, BCR immunoglobulin editing ensures that a second V-J rearrangement occurs. This helps to maintain tolerance, by generating a novel BCR with a new antigenic specificity. We report that human B cells can, surprisingly, undergo type 2 replacement associated with κ light-chain rearrangements. The de novo IGKV-IGKJ products result from the partial replacement of a previously rearranged IGKV gene by a new germline IGKV gene, in-frame and without deletion or addition of nucleotides. There are wrcy/rgyw motifs at the 'IGKV donor-IGKV recipient chimera junction' as described for type 2 IGHV replacement, but activation-induced cytidine deaminase (AID) expression was not detected. This unusual mechanism of homologous recombination seems to be a variant of gene conversion-like recombination, which does not require AID. The recombination phenomenon described here provides new insight into immunoglobulin locus recombination and BCR immunoglobulin repertoire diversity.

KEYWORDS:

AICDA; B-cell receptor immunoglobulin repertoire diversity; IGKV replacement; gene conversion-like recombination; immunoglobulin genes; immunoglobulin κ

PMID:
24134819
PMCID:
PMC3904247
DOI:
10.1111/imm.12192
[Indexed for MEDLINE]
Free PMC Article
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