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
Vassiliou, George S
Smith, Kenneth GC
Lyons, Paul A
Russell, Colin A
Anderson, Carl A
Kellam, Paul
Bashford-Rogers, Rachael JM
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. S., Smith, K. G., Lyons, P. A., 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 cells, B-cell receptor seq, chronic lymphocytic leukemia, isotype switching, repertoire analysis, B-Lymphocytes, Gene Rearrangement, B-Lymphocyte, Humans, Immunoglobulin Class Switching, Immunoglobulin Isotypes, Immunoglobulin Joining Region, Immunoglobulin Variable Region, Leukemia, Lymphocytic, Chronic, B-Cell, Leukocytes, Mononuclear, Multigene Family, Receptors, Antigen, B-Cell, Somatic Hypermutation, Immunoglobulin
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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