TY - JOUR
T1 - Combined influence of B-cell receptor rearrangement and somatic hypermutation on B-cell class-switch fate in health and in chronic lymphocytic leukemia
AU - Petrova, Velislava N.
AU - Muir, Luke
AU - McKay, Paul F.
AU - Vassiliou, George S.
AU - Smith, Kenneth G. C.
AU - Lyons, Paul A.
AU - Russell, Colin A.
AU - Anderson, Carl A.
AU - Kellam, Paul
AU - Bashford-Rogers, Rachael J. M.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85054930858&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/30147686
U2 - https://doi.org/10.3389/fimmu.2018.01784
DO - https://doi.org/10.3389/fimmu.2018.01784
M3 - Article
C2 - 30147686
SN - 1664-3224
VL - 9
JO - Frontiers in immunology
JF - Frontiers in immunology
IS - AUG
M1 - 1784
ER -