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Frequency and genetic characterization of V(DD)J recombinants in the human peripheral blood antibody repertoire.
- Source :
-
Immunology [Immunology] 2012 Sep; Vol. 137 (1), pp. 56-64. - Publication Year :
- 2012
-
Abstract
- Antibody heavy-chain recombination that results in the incorporation of multiple diversity (D) genes, although uncommon, contributes substantially to the diversity of the human antibody repertoire. Such recombination allows the generation of heavy chain complementarity determining region 3 (HCDR3) regions of extreme length and enables junctional regions that, because of the nucleotide bias of N-addition regions, are difficult to produce through normal V(D)J recombination. Although this non-classical recombination process has been observed infrequently, comprehensive analysis of the frequency and genetic characteristics of such events in the human peripheral blood antibody repertoire has not been possible because of the rarity of such recombinants and the limitations of traditional sequencing technologies. Here, through the use of high-throughput sequencing of the normal human peripheral blood antibody repertoire, we analysed the frequency and genetic characteristics of V(DD)J recombinants. We found that these recombinations were present in approximately 1 in 800 circulating B cells, and that the frequency was severely reduced in memory cell subsets. We also found that V(DD)J recombination can occur across the spectrum of diversity genes, indicating that virtually all recombination signal sequences that flank diversity genes are amenable to V(DD)J recombination. Finally, we observed a repertoire bias in the diversity gene repertoire at the upstream (5') position, and discovered that this bias was primarily attributable to the order of diversity genes in the genomic locus.<br /> (© 2012 The Authors. Immunology © 2012 Blackwell Publishing Ltd.)
- Subjects :
- Amino Acid Sequence
Antibodies blood
Base Sequence
Complementarity Determining Regions genetics
Genetic Variation
High-Throughput Nucleotide Sequencing
Humans
Immunoglobulin Variable Region genetics
Sequence Alignment
Sequence Analysis, DNA
Antibodies genetics
Antibody Formation genetics
B-Lymphocytes immunology
Gene Frequency
V(D)J Recombination genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1365-2567
- Volume :
- 137
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 22612413
- Full Text :
- https://doi.org/10.1111/j.1365-2567.2012.03605.x