Commonality despite exceptional diversity in the baseline human antibody repertoire
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 di...
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| Published in | Nature (London) Vol. 566; no. 7744; pp. 393 - 397 |
|---|---|
| Main Authors | , , , |
| Format | Journal Article |
| Language | English |
| Published |
London
Nature Publishing Group UK
01.02.2019
Nature Publishing Group |
| Subjects | |
| Online Access | Get full text |
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| Abstract | 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.
A genetic study of the baseline human antibody repertoire, based on the circulating B cell populations of ten subjects, reveals universally shared antibody clonotypes within repertoires that are largely unique to the individual. |
|---|---|
| AbstractList | 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 exposure1. The diversity of the naive antibody repertoire in humans is estimated to be at least 1012 unique antibodies2. Because the number of peripheral blood B cells in a healthy adult human is on the order of 5 × 109, 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 cells3. 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.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 exposure1. The diversity of the naive antibody repertoire in humans is estimated to be at least 1012 unique antibodies2. Because the number of peripheral blood B cells in a healthy adult human is on the order of 5 × 109, 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 cells3. 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. 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 . The diversity of the naive antibody repertoire in humans is estimated to be at least 10 unique antibodies . Because the number of peripheral blood B cells in a healthy adult human is on the order of 5 × 10 , 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 . 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. 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. The diversity of the naive antibody repertoire in humans is estimated to be at least 1012 unique antibodies. Because the number of peripheral blood B cells in a healthy adult human is on the order of 5 × 109, 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. 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. 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.sup.1. The diversity of the naive antibody repertoire in humans is estimated to be at least 10.sup.12 unique antibodies.sup.2. Because the number of peripheral blood B cells in a healthy adult human is on the order of 5 × 10.sup.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.sup.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. 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.sup.1. The diversity of the naive antibody repertoire in humans is estimated to be at least 10.sup.12 unique antibodies.sup.2. Because the number of peripheral blood B cells in a healthy adult human is on the order of 5 × 10.sup.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.sup.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. A genetic study of the baseline human antibody repertoire, based on the circulating B cell populations of ten subjects, reveals universally shared antibody clonotypes within repertoires that are largely unique to the individual. 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. A genetic study of the baseline human antibody repertoire, based on the circulating B cell populations of ten subjects, reveals universally shared antibody clonotypes within repertoires that are largely unique to the individual. |
| Audience | Academic |
| Author | Inderbitzin, Anne Briney, Bryan Burton, Dennis R. Joyce, Collin |
| AuthorAffiliation | 4 IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA 2 Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA 3 Center for Viral Systems Biology, The Scripps Research Institute, La Jolla, CA 92037, USA 6 Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02129, USA 1 Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA 5 Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland |
| AuthorAffiliation_xml | – name: 2 Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA – name: 6 Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02129, USA – name: 1 Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA – name: 5 Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland – name: 3 Center for Viral Systems Biology, The Scripps Research Institute, La Jolla, CA 92037, USA – name: 4 IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA |
| Author_xml | – sequence: 1 givenname: Bryan surname: Briney fullname: Briney, Bryan email: briney@scripps.edu organization: Department of Immunology and Microbiology, The Scripps Research Institute, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, Center for Viral Systems Biology, The Scripps Research Institute, IAVI Neutralizing Antibody Center, The Scripps Research Institute, Human Vaccines Project – sequence: 2 givenname: Anne surname: Inderbitzin fullname: Inderbitzin, Anne organization: Department of Immunology and Microbiology, The Scripps Research Institute, Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich – sequence: 3 givenname: Collin surname: Joyce fullname: Joyce, Collin organization: Department of Immunology and Microbiology, The Scripps Research Institute, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, Center for Viral Systems Biology, The Scripps Research Institute, IAVI Neutralizing Antibody Center, The Scripps Research Institute – sequence: 4 givenname: Dennis R. surname: Burton fullname: Burton, Dennis R. email: burton@scripps.edu organization: Department of Immunology and Microbiology, The Scripps Research Institute, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, IAVI Neutralizing Antibody Center, The Scripps Research Institute, Human Vaccines Project, Ragon Institute of MGH, MIT and Harvard |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/30664748$$D View this record in MEDLINE/PubMed |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 AUTHOR CONTRIBUTIONS BB and DRB planned and designed the experiments. BB, AI and CJ performed experiments. BB analyzed data. BB and DRB wrote the manuscript. All authors contributed to manuscript revisions. |
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| SubjectTerms | 45/23 45/77 631/250/2152/2153/1291 631/250/2152/2497 Adaptive systems Analysis Antibodies Antibodies - chemistry Antibodies - genetics Antibodies - immunology Antibody response Antigens Antigens - immunology Autoantigens B cells B-Lymphocytes - cytology B-Lymphocytes - immunology B-Lymphocytes - metabolism Base Sequence Clone Cells - cytology Clone Cells - immunology Clone Cells - metabolism Commonality Estimates Gene sequencing Genes Genetic research Genetic Variation - genetics Genomes Genomics Human genome Human physiology Humanities and Social Sciences Humans Immune system Letter Library collections Lymphocytes Lymphocytes B Lymphocytes T Multiculturalism & pluralism multidisciplinary Organs Peripheral blood Population Science Science (multidisciplinary) Sequence Analysis, DNA Somatic hypermutation T cell receptors T cells |
| Title | Commonality despite exceptional diversity in the baseline human antibody repertoire |
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