Understanding the human antibody repertoire
Open accessAbstract
The origins of the various elements in the human antibody repertoire have been and still are subject to considerable uncertainty. Uncertainty in respect of whether the various elements have always served a specific defense function or whether they were co-opted from other organismal roles to form a crude naïve repertoire that then became more complex as combinatorial mechanisms were added. Estimates of the current size of the human antibody naïve repertoire are also widely debated with numbers anywhere from 10 million members, based on experimentally derived numbers, to in excess of one thousand trillion members or more, based on the different sequences derived from theoretical combinatorial calculations. There are questions that are relevant at both ends of this number spectrum. At the lower bound it could be questioned whether this is an insufficient repertoire size to counter all the potential antigen-bearing pathogens. At the upper bound the question is rather simpler: How can any individual interrogate such an astronomical number of antibody-bearing B cells in a timeframe that is meaningful? This review evaluates the evolutionary aspects of the adaptive immune system, the calculations that lead to the large repertoire estimates, some of the experimental evidence pointing to a more restricted repertoire whose variation appears to derive from convergent 'structure and specificity features', and includes a theoretical model that seems to support it. Finally, a solution that may reconcile the size difference anomaly, which is still a hot subject of debate, is suggested.
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In the human immune system, antibodies are produced by B cells and the repertoire is estimated at approximately 10^13 unique sequences.
“In the human immune system, antibodies are produced by B cells and its repertoire is estimated at approximately 10 13 unique sequences [7].”
From Computational and artificial intelligence-based methods for antibody development (2023) · cites this paper as [7]
Each antibody chain is encoded by multiple gene segments (V, D, and J segments), which are spliced together using a V(D)J recombination process.
“Each of the chains is encoded by multiple gene segments (V, D, and J segments), which are spliced together using a V(D)J recombination process [7].”
From Computational and artificial intelligence-based methods for antibody development (2023) · cites this paper as [7]
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Computational and artificial intelligence-based methods for antibody development
Kim, J., McFee, M., Fang, Q., Abdin, O., & Kim, P. M. (2023) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2022.12.005 · Cited by 178 · see citing works
- Authors
- Rees, A. R.
- Affiliations
- Rees Consulting AB
- Corresponding author
- Rees, Anthony R
- ORCID
- Rees, Anthony R
- Venue
- mAbs
- Publisher
- Informa UK Limited
- Published
- 2020-01
- Volume
- 12
- Issue
- 1
- Pages
- 1729683-1729683
- ISSN
- 1942-0862 (ISSN-L)
- 1942-0870
- PMC
- PMC7153836
- OpenAlex
- W3008570337
- Cited by
- 108
- References
- 85
- Citations by year
- 2026: 13 · 2025: 23 · 2024: 17 · 2023: 16 · 2022: 11 · 2021: 20 · 2020: 7 · 2019: 1
- FWCI
- 1.32
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- mAbs (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- 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
- human antibody repertoire, adaptive immunity evolution, convergent evolution
- MeSH terms
- Antibody Formation, Humans
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