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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Glanville, Jacob Tsaban, Lea Pons, Jaume Benichou, Jennifer Prak, Eline T. Luning Azran, Roy Desmarais, Cindy Louzoun, Yoram Kuo, Tracy C. |
| Description | Country affiliation: Israel Author Affiliation: Benichou J ( Mina and Everard Goodman Faculty of Life Sciences, Bar Ilan University, Ramat Gan 52900, Israel.) |
| Abstract | The Ab repertoire is not uniform. Some variable, diversity, and joining genes are used more frequently than others. Nonuniform usage can result from the rearrangement process, or from selection. To study how the Ab repertoire is selected, we analyzed one part of diversity generation that cannot be driven by the rearrangement mechanism: the reading frame usage of DH genes. We have used two high-throughput sequencing methodologies, multiple subjects and advanced algorithms to measure the DH reading frame usage in the human Ab repertoire. In most DH genes, a single reading frame is used predominantly, and inverted reading frames are practically never observed. The choice of a single DH reading frame is not limited to a single position of the DH gene. Rather, each DH gene participates in rearrangements of differing CDR3 lengths, restricted to multiples of three. In nonproductive rearrangements, there is practically no reading frame bias, but there is still a striking absence of inversions. Biases in DH reading frame usage are more pronounced, but also exhibit greater interindividual variation, in IgG(+) and IgA(+) than in IgM(+) B cells. These results suggest that there are two developmental checkpoints of DH reading frame selection. The first occurs during VDJ recombination, when inverted DH genes are usually avoided. The second checkpoint occurs after rearrangement, once the BCR is expressed. The second checkpoint implies that DH reading frames are subjected to differential selection. Following these checkpoints, clonal selection induces a host-specific DH reading frame usage bias. |
| ISSN | 00221767 |
| e-ISSN | 15506606 |
| DOI | 10.4049/jimmunol.1201929 |
| Journal | The Journal of Immunology |
| Issue Number | 11 |
| Volume Number | 190 |
| Language | English |
| Publisher | The American Association of Immunologists |
| Publisher Date | 2013-06-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Antibody Diversity Genetics Complementarity Determining Regions Immunoglobulin Heavy Chains Amino Acid Sequence B-lymphocyte Subsets Metabolism Codon, Terminator Chemistry Gene Expression Gene Rearrangement High-throughput Nucleotide Sequencing Immunoglobulin A Immunoglobulin G Immunoglobulin Joining Region Immunoglobulin M Immunoglobulin Variable Region Reading Frames Reproducibility Of Results V(d)j Recombination Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Immunology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
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