High frequency of shared clonotypes in human B cell receptor repertoires
Open accessAbstract
The human genome contains approximately 20 thousand protein-coding genes 1, 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.
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Despite vast numbers of diverse sequences in a typical human antibody repertoire, a non-trivial amount of these is shared between individuals.
“From a sequence perspective, it was demonstrated recently that despite the vast numbers of diverse sequences in a typical human antibody repertoire, a non-trivial amount of these is shared between individuals [23, 223].”
From Computational approaches to therapeutic antibody design: established methods and emerging trends (2020) · cites this paper as [223]
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- Authors
- Soto, C., Bombardi, R. G., Branchizio, A., Kose, N., Matta, P., Sevy, A. M., Sinkovits, R. S., Gilchuk, P., Finn, J. A., & Crowe, J. E.
- Affiliations
- Vanderbilt University Medical Center (US)
- Vanderbilt University (US)
- San Diego Supercomputer Center (US)
- Corresponding author
- Crowe, James E.
- ORCID
- Venue
- Nature
- Published
- 2019-02
- Volume
- 566
- Issue
- 7744
- Pages
- 398-402
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC6949180
- OpenAlex
- W2911980279
- Cited by
- 294
- References
- 28
- Citations by year
- 2026: 19 · 2025: 26 · 2024: 35 · 2023: 37 · 2022: 54 · 2021: 52 · 2020: 51 · 2019: 20
- FWCI
- 17.65
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institutes of Health (U42OD011158)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Physical Sciences › Engineering › Biomedical Engineering › Artificial Immune Systems Applications
- Keywords
- B cell receptor repertoire, B cell clonotypes, heavy chain variable region, light chain variable region, V(D)J recombination, clonotype diversity, umbilical cord blood, adaptive immunity
- MeSH terms
- Adult, Amino Acid Sequence, Antibodies, Antigens, B-Lymphocytes, Base Sequence, Clone Cells, Female, Fetal Blood, Humans, Infant, Newborn, Male, Receptors, Antigen, B-Cell, Sequence Analysis, DNA, Healthy Volunteers
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