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Commonality despite exceptional diversity in the baseline human antibody repertoire
Open accessAbstract
In principle, humans can produce an antibody response to any non-self-antigen molecule in the appropriate context. This flexibility is achieved by the presence of a large repertoire of naive antibodies, the diversity of which is expanded by somatic hypermutation following antigen exposure 1. The diversity of the naive antibody repertoire in humans is estimated to be at least 10 12 unique antibodies 2. Because the number of peripheral blood B cells in a healthy adult human is on the order of 5 × 10 9, the circulating B cell population samples only a small fraction of this diversity. Full-scale analyses of human antibody repertoires have been prohibitively difficult, primarily owing to their massive size. The amount of information encoded by all of the rearranged antibody and T cell receptor genes in one person-the 'genome' of the adaptive immune system-exceeds the size of the human genome by more than four orders of magnitude. Furthermore, because much of the B lymphocyte population is localized in organs or tissues that cannot be comprehensively sampled from living subjects, human repertoire studies have focused on circulating B cells 3. Here we examine the circulating B cell populations of ten human subjects and present what is, to our knowledge, the largest single collection of adaptive immune receptor sequences described to date, comprising almost 3 billion antibody heavy-chain sequences. This dataset enables genetic study of the baseline human antibody repertoire at an unprecedented depth and granularity, which reveals largely unique repertoires for each individual studied, a subpopulation of universally shared antibody clonotypes, and an exceptional overall diversity of the antibody repertoire.
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“NGS provides a snapshot of millions of antibody sequences sampled from the theoretically possible 1012–1015 antibody sequences in a human repertoire [23, 24].”
From Computational approaches to therapeutic antibody design: established methods and emerging trends (2020) · cites this paper as [23]
In the citing paper
“Together with the diversity introduced by V(D) J recombination, somatic hypermutation can produce an estimated 1012–1015 possible antibody sequences [23, 24].”
From Computational approaches to therapeutic antibody design: established methods and emerging trends (2020) · cites this paper as [23]
In the citing paper
“Each of the estimated 5 × 109 B-cells in an organism [23] produces a distinct B-cell receptor (membrane-bound) or antibody (in soluble form) through somatic recombination of variable (V), diversity (D), joining (J) and constant (C) gene segments [28, 29].”
From Computational approaches to therapeutic antibody design: established methods and emerging trends (2020) · cites this paper as [23]
In the citing paper
“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 [23]
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Metadata
- Authors
- Briney, B., Inderbitzin, A., Joyce, C., & Burton, D. R.
- Affiliations
- Scripps Research Institute (US)
- Corresponding author
- Briney, Bryan
- Burton, Dennis R.
- Venue
- Nature
- Published
- 2019-01-21
- Volume
- 566
- Issue
- 7744
- Pages
- 393-397
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC6411386
- OpenAlex
- W2910384850
- Cited by
- 544
- References
- 24
- Citations by year
- 2026: 65 · 2025: 79 · 2024: 60 · 2023: 81 · 2022: 77 · 2021: 83 · 2020: 65 · 2019: 34
- FWCI
- 25.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- International AIDS Vaccine Initiative (SFP1849)
- Ragon Institute of MGH, MIT and Harvard
- National Institute of Allergy and Infectious Diseases (UM1AI100663, U19AI135995)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Keywords
- human antibody repertoire, naive B cells, repertoire diversity, adaptive immunity, somatic hypermutation
- MeSH terms
- Antibodies, Antigens, B-Lymphocytes, Base Sequence, Clone Cells, Humans, Genetic Variation, Sequence Analysis, DNA
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