High frequency of shared clonotypes in human B cell receptor repertoires
Top Cited Papers
- 13 February 2019
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature
- Vol. 566 (7744), 398-402
- https://doi.org/10.1038/s41586-019-0934-8
Abstract
The human genome contains approximately 20 thousand protein-coding genes1, but the size of the collection of antigen receptors of the adaptive immune system that is generated by the recombination of gene segments with non-templated junctional additions (on B cells) is unknown—although it is certainly orders of magnitude larger. It has not been established whether individuals possess unique (or private) repertoires or substantial components of shared (or public) repertoires. Here we sequence recombined and expressed B cell receptor genes in several individuals to determine the size of their B cell receptor repertoires, and the extent to which these are shared between individuals. Our experiments revealed that the circulating repertoire of each individual contained between 9 and 17 million B cell clonotypes. The three individuals that we studied shared many clonotypes, including between 1 and 6% of B cell heavy-chain clonotypes shared between two subjects (0.3% of clonotypes shared by all three) and 20 to 34% of λ or κ light chains shared between two subjects (16 or 22% of λ or κ light chains, respectively, were shared by all three). Some of the B cell clonotypes had thousands of clones, or somatic variants, within the clonotype lineage. Although some of these shared lineages might be driven by exposure to common antigens, previous exposure to foreign antigens was not the only force that shaped the shared repertoires, as we also identified shared clonotypes in umbilical cord blood samples and all adult repertoires. The unexpectedly high prevalence of shared clonotypes in B cell repertoires, and identification of the sequences of these shared clonotypes, should enable better understanding of the role of B cell immune repertoires in health and disease.This publication has 30 references indexed in Scilit:
- IgBLAST: an immunoglobulin variable domain sequence analysis toolNucleic Acids Research, 2013
- A recurring motif for antibody recognition of the receptor-binding site of influenza hemagglutininNature Structural & Molecular Biology, 2013
- High-throughput sequencing of the paired human immunoglobulin heavy and light chain repertoireNature Biotechnology, 2013
- Epitope-Specific Human Influenza Antibody Repertoires Diversify by B Cell Intraclonal Sequence Divergence and Interclonal ConvergenceThe Journal of Immunology, 2011
- High-Resolution Description of Antibody Heavy-Chain Repertoires in HumansPLOS ONE, 2011
- Rapid generation of fully human monoclonal antibodies specific to a vaccinating antigenNature Protocols, 2008
- WebLogo: A Sequence Logo Generator: Figure 1Genome Research, 2004
- Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: Report of the BIOMED-2 Concerted Action BMH4-CT98-3936Leukemia, 2003
- The immunomeMolecular Immunology, 1999