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: | Journal article |
| Language: | English |
| Published: |
Frontiers Media
2018
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| _version_ | 1826277177446891520 |
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| author | Petrova, V Muir, L McKay, P Vassiliou, G Smith, K Lyons, P Russell, C Anderson, C Kellam, P Bashford-Rogers, R |
| author_facet | Petrova, V Muir, L McKay, P Vassiliou, G Smith, K Lyons, P Russell, C Anderson, C Kellam, P Bashford-Rogers, R |
| author_sort | Petrova, V |
| collection | OXFORD |
| 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 | 2024-03-06T23:24:59Z |
| format | Journal article |
| id | oxford-uuid:6a0d131b-1722-4831-8b5f-70a042cf072c |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:24:59Z |
| publishDate | 2018 |
| publisher | Frontiers Media |
| record_format | dspace |
| spelling | oxford-uuid:6a0d131b-1722-4831-8b5f-70a042cf072c2022-03-26T18:55:00ZCombined influence of B-cell receptor rearrangement and somatic hypermutation on B-cell class-switch fate in health and in chronic lymphocytic leukemiaJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:6a0d131b-1722-4831-8b5f-70a042cf072cEnglishSymplectic Elements at OxfordFrontiers Media2018Petrova, VMuir, LMcKay, PVassiliou, GSmith, KLyons, PRussell, CAnderson, CKellam, PBashford-Rogers, RA 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. |
| spellingShingle | Petrova, V Muir, L McKay, P Vassiliou, G Smith, K Lyons, P Russell, C Anderson, C Kellam, P Bashford-Rogers, R Combined influence of B-cell receptor rearrangement and somatic hypermutation on B-cell class-switch fate in health and in chronic lymphocytic leukemia |
| 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 |
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