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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.

Original publication

DOI

10.3389/fimmu.2018.01784

Type

Journal article

Journal

Front Immunol

Publication Date

2018

Volume

9

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