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Commonality despite exceptional diversity in the baseline human antibody repertoire


Briney, Bryan; Inderbitzin, Anne; Joyce, Collin; Burton, Dennis R (2019). Commonality despite exceptional diversity in the baseline human antibody repertoire. Nature, 566(7744):393-397.

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.

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.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Infectious Diseases
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Health Sciences > Multidisciplinary
Language:English
Date:February 2019
Deposited On:06 Feb 2020 08:12
Last Modified:29 Jul 2020 13:25
Publisher:Springer
ISSN:0028-0836
OA Status:Green
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1038/s41586-019-0879-y
PubMed ID:30664748

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