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
Velislava N PetrovaRachael J M Bashford-Rogers

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.

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Citations

Sep 27, 2019·Nature·R J M Bashford-RogersK G C Smith
Jun 21, 2020·Nature Communications·Igor MandricSerghei Mangul
Feb 19, 2020·Nature Immunology·Kylie R JamesSarah A Teichmann

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Datasets Mentioned

BETA
EGAS00001002634
EGAS00001002633

Methods Mentioned

BETA
PCR
FACS
FCS

Software Mentioned

Celgene
QUEST
BLAST
FlowJo

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