The evolution within us
Open accessAbstract
The B-cell immune response is a remarkable evolutionary system found in jawed vertebrates. B-cell receptors, the membrane-bound form of antibodies, are capable of evolving high affinity to almost any foreign protein. High germline diversity and rapid evolution upon encounter with antigen explain the general adaptability of B-cell populations, but the dynamics of repertoires are less well understood. These dynamics are scientifically and clinically important. After highlighting the remarkable characteristics of naive and experienced B-cell repertoires, especially biased usage of genes encoding the B-cell receptors, we contrast methods of sequence analysis and their attempts to explain patterns of B-cell evolution. These phylogenetic approaches are currently unlinked to explicit models of B-cell competition, which analyse repertoire evolution at the level of phenotype, the affinities and specificities to particular antigenic sites. The models, in turn, suggest how chance, infection history and other factors contribute to different patterns of immunodominance and protection between people. Challenges in rational vaccine design, specifically vaccines to induce broadly neutralizing antibodies to HIV, underscore critical gaps in our understanding of B cells' evolutionary and ecological dynamics.
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The adaptive immune system of vertebrates functions largely by recognition of foreign peptide sequences, which are directly recognized by the B cell surface Ig receptor and are also loaded into MHC molecules to be presented to specific T-cell receptors.
“The adaptive immune system of vertebrate organisms functions largely by recognition of foreign peptide sequences, which are directly recognized by the B cell surface Ig receptor (584 -585), and are also loaded into the grooves of the major histocompatibility receptors to be presented to speci fi c T-cell receptors (586).”
From Biological roles of glycans (2017) · cites this paper as [584]
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Varki, A. (2017) · Glycobiology · doi:10.1093/glycob/cww086 · Cited by 2,635 · see citing works
“receptor (584, 585), and are also loaded into the grooves of the major histocompatibility receptors to be”
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- Authors
- Cobey, S., Wilson, P., & Matsen, F. A.
- Affiliations
- University of Chicago (US)
- Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
- Corresponding author
- Cobey, Sarah
- Venue
- Philosophical Transactions of the Royal Society B: Biological Sciences
- Publisher
- The Royal Society
- Published
- 2015-09-05
- Volume
- 370
- Issue
- 1676
- Pages
- 20140235
- ISSN
- 0962-8436 (ISSN-L)
- 1471-2970
- PMC
- PMC4528412
- OpenAlex
- W1928797414
- Cited by
- 40
- References
- 144
- Citations by year
- 2026: 2 · 2025: 3 · 2023: 1 · 2022: 8 · 2021: 4 · 2020: 3 · 2019: 5 · 2018: 3 · 2017: 8 · 2016: 3
- FWCI
- 0.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Philosophical Transactions of the Royal Society B Biological Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- James S. McDonnell Foundation
- University of Washington
- National Institutes of Health (HHSN272201400005C, NIH-R01)
- U.S. Public Health Service (HHSN272201400005C)
- Center for AIDS Research, University of Washington (P30 AI027757)
- National Institute on Aging
- National Heart, Lung, and Blood Institute (NIH R01)
- National Institute of Mental Health
- National Institute on Drug Abuse
- National Cancer Institute
- National Institute of General Medical Sciences (R01GM113246)
- National Institute of Allergy and Infectious Diseases (DP2AI117921, U19AI109946, P01AI097092, HHSN272201400005C, U19AI090023, U19AI082724, P30AI027757, U19AI057266)
- National Institute of Diabetes and Digestive and Kidney Diseases (NIH R01)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Keywords
- naive B cells, immunodominance, B cell affinity maturation, HIV broadly neutralizing antibodies, vaccine design, jawed vertebrates
- MeSH terms
- Animals, B-Lymphocytes, Humans, Immunity, Innate, Models, Genetic, Receptors, Antigen, B-Cell, Models, Statistical, Models, Immunological, Evolution, Molecular, Somatic Hypermutation, Immunoglobulin, Adaptive Immunity, Antibodies, Neutralizing
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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