Combined Influence of B-Cell Receptor Rearrangement and Somatic Hypermutation on B-Cell Class-Switch Fate in Health and in Chronic Lymphocytic Leukemia
A diverse B-cell receptor (BCR) repertoire is required to bind a wide range of antigens. BCRs are generated through genetic recombination and can be diversified through somatic hypermutation (SHM) or class-switch recombination (CSR). Patterns of repertoire diversity can vary substantially between di...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.01784/full |
| _version_ | 1818898312384741376 |
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| author | Velislava N. Petrova Luke Muir Paul F. McKay George S. Vassiliou Kenneth G. C. Smith Paul A. Lyons Colin A. Russell Carl A. Anderson Paul Kellam Rachael J. M. Bashford-Rogers |
| author_facet | Velislava N. Petrova Luke Muir Paul F. McKay George S. Vassiliou Kenneth G. C. Smith Paul A. Lyons Colin A. Russell Carl A. Anderson Paul Kellam Rachael J. M. Bashford-Rogers |
| author_sort | Velislava N. Petrova |
| collection | DOAJ |
| description | A diverse B-cell receptor (BCR) repertoire is required to bind a wide range of antigens. BCRs are generated through genetic recombination and can be diversified through somatic hypermutation (SHM) or class-switch recombination (CSR). Patterns of repertoire diversity can vary substantially between different health conditions. We use isotype-resolved BCR sequencing to compare B-cell evolution and class-switch fate in healthy individuals and in patients with chronic lymphocytic leukemia (CLL). We show that the patterns of SHM and CSR in B-cells from healthy individuals are distinct from CLL. We identify distinct properties of clonal expansion that lead to the generation of antibodies of different classes in healthy, malignant, and non-malignant CLL BCR repertoires. We further demonstrate that BCR diversity is affected by relationships between antibody variable and constant regions leading to isotype-specific signatures of variable gene usage. This study provides powerful insights into the mechanisms underlying the evolution of the adaptive immune responses in health and their aberration during disease. |
| first_indexed | 2024-12-19T19:30:04Z |
| format | Article |
| id | doaj.art-b6c963f72e5647b2ac02634b482d23a7 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-19T19:30:04Z |
| publishDate | 2018-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-b6c963f72e5647b2ac02634b482d23a72022-12-21T20:08:37ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-08-01910.3389/fimmu.2018.01784371933Combined Influence of B-Cell Receptor Rearrangement and Somatic Hypermutation on B-Cell Class-Switch Fate in Health and in Chronic Lymphocytic LeukemiaVelislava N. Petrova0Luke Muir1Paul F. McKay2George S. Vassiliou3Kenneth G. C. Smith4Paul A. Lyons5Colin A. Russell6Carl A. Anderson7Paul Kellam8Rachael J. M. Bashford-Rogers9The Wellcome Sanger Institute, Hinxton, United KingdomDepartment of Medicine, Division of Infectious Diseases, Imperial College London, London, United KingdomDepartment of Medicine, Division of Infectious Diseases, Imperial College London, London, United KingdomThe Wellcome Sanger Institute, Hinxton, United KingdomDepartment of Medicine, University of Cambridge, Cambridge, United KingdomDepartment of Medicine, University of Cambridge, Cambridge, United KingdomDepartment of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam, NetherlandsThe Wellcome Sanger Institute, Hinxton, United KingdomDepartment of Medicine, Division of Infectious Diseases, Imperial College London, London, United KingdomDepartment of Medicine, University of Cambridge, Cambridge, United KingdomA diverse B-cell receptor (BCR) repertoire is required to bind a wide range of antigens. BCRs are generated through genetic recombination and can be diversified through somatic hypermutation (SHM) or class-switch recombination (CSR). Patterns of repertoire diversity can vary substantially between different health conditions. We use isotype-resolved BCR sequencing to compare B-cell evolution and class-switch fate in healthy individuals and in patients with chronic lymphocytic leukemia (CLL). We show that the patterns of SHM and CSR in B-cells from healthy individuals are distinct from CLL. We identify distinct properties of clonal expansion that lead to the generation of antibodies of different classes in healthy, malignant, and non-malignant CLL BCR repertoires. We further demonstrate that BCR diversity is affected by relationships between antibody variable and constant regions leading to isotype-specific signatures of variable gene usage. This study provides powerful insights into the mechanisms underlying the evolution of the adaptive immune responses in health and their aberration during disease.https://www.frontiersin.org/article/10.3389/fimmu.2018.01784/fullB-cell receptor seqchronic lymphocytic leukemiaisotype switchingB cellsrepertoire analysis |
| spellingShingle | Velislava N. Petrova Luke Muir Paul F. McKay George S. Vassiliou Kenneth G. C. Smith Paul A. Lyons Colin A. Russell Carl A. Anderson Paul Kellam Rachael J. M. Bashford-Rogers Combined Influence of B-Cell Receptor Rearrangement and Somatic Hypermutation on B-Cell Class-Switch Fate in Health and in Chronic Lymphocytic Leukemia Frontiers in Immunology B-cell receptor seq chronic lymphocytic leukemia isotype switching B cells repertoire analysis |
| title | Combined Influence of B-Cell Receptor Rearrangement and Somatic Hypermutation on B-Cell Class-Switch Fate in Health and in Chronic Lymphocytic Leukemia |
| title_full | Combined Influence of B-Cell Receptor Rearrangement and Somatic Hypermutation on B-Cell Class-Switch Fate in Health and in Chronic Lymphocytic Leukemia |
| title_fullStr | Combined Influence of B-Cell Receptor Rearrangement and Somatic Hypermutation on B-Cell Class-Switch Fate in Health and in Chronic Lymphocytic Leukemia |
| title_full_unstemmed | Combined Influence of B-Cell Receptor Rearrangement and Somatic Hypermutation on B-Cell Class-Switch Fate in Health and in Chronic Lymphocytic Leukemia |
| title_short | Combined Influence of B-Cell Receptor Rearrangement and Somatic Hypermutation on B-Cell Class-Switch Fate in Health and in Chronic Lymphocytic Leukemia |
| title_sort | combined influence of b cell receptor rearrangement and somatic hypermutation on b cell class switch fate in health and in chronic lymphocytic leukemia |
| topic | B-cell receptor seq chronic lymphocytic leukemia isotype switching B cells repertoire analysis |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.01784/full |
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