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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Authors
Petrova, Velislava N
Muir, Luke
McKay, Paul F
Russell, Colin A
Anderson, Carl A
Kellam, Paul
Publication Date
2018Journal Title
Front Immunol
ISSN
1664-3224
Publisher
Frontiers Media SA
Volume
9
Pages
1784
Language
eng
Type
Article
Physical Medium
Electronic-eCollection
Metadata
Show full item recordCitation
Petrova, V. N., Muir, L., McKay, P. F., Vassiliou, G., Smith, K., Lyons, P., Russell, C. A., et al. (2018). Combined Influence of B-Cell Receptor Rearrangement and Somatic Hypermutation on B-Cell Class-Switch Fate in Health and in Chronic Lymphocytic Leukemia.. Front Immunol, 9 1784. https://doi.org/10.3389/fimmu.2018.01784
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.
Keywords
B-Lymphocytes, Leukocytes, Mononuclear, Humans, Immunoglobulin Joining Region, Immunoglobulin Variable Region, Receptors, Antigen, B-Cell, Immunoglobulin Isotypes, Gene Rearrangement, B-Lymphocyte, Immunoglobulin Class Switching, Somatic Hypermutation, Immunoglobulin, Multigene Family, Leukemia, Lymphocytic, Chronic, B-Cell
Sponsorship
Wellcome Trust
Funder references
Medical Research Council (MC_PC_12009)
Wellcome Trust (083650/Z/07/Z)
Wellcome Trust (106068/Z/14/Z)
Medical Research Council (MR/L019027/1)
Identifiers
External DOI: https://doi.org/10.3389/fimmu.2018.01784
This record's URL: https://www.repository.cam.ac.uk/handle/1810/284566
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