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Characterization of a new V gene replacement in the absence of activation-induced cytidine deaminase and its contribution to human B-cell receptor diversity.
- Source :
- Immunology; Feb2014, Vol. 141 Issue 2, p268-275, 8p
- Publication Year :
- 2014
-
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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00192805
- Volume :
- 141
- Issue :
- 2
- Database :
- Complementary Index
- Journal :
- Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 93568789
- Full Text :
- https://doi.org/10.1111/imm.12192