Petrova, VN;
Muir, L;
McKay, PF;
Vassiliou, GS;
Smith, KGC;
Lyons, PA;
Russell, CA;
... Bashford-Rogers, RJM; + view all
(2018)
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
, 9
, Article 1784. 10.3389/fimmu.2018.01784.
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Abstract
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.
| Type: | Article |
|---|---|
| Title: | Combined Influence of B-Cell Receptor Rearrangement and Somatic Hypermutation on B-Cell Class-Switch Fate in Health and in Chronic Lymphocytic Leukemia |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3389/fimmu.2018.01784 |
| Publisher version: | https://doi.org/10.3389/fimmu.2018.01784 |
| Language: | English |
| Additional information: | Copyright © 2018 Petrova, Muir, McKay, Vassiliou, Smith, Lyons, Russell, Anderson, Kellam and Bashford-Rogers. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. https://creativecommons.org/licenses/by/4.0/ |
| Keywords: | B-cell receptor seq, chronic lymphocytic leukemia, isotype switching, B cells, repertoire analysis |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10094020 |
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