Inferring processes underlying B-cell repertoire diversity

We quantify the VDJ recombination and somatic hypermutation processes in human B cells using probabilistic inference methods on high-throughput DNA sequence repertoires of human B-cell receptor heavy chains. Our analysis captures the statistical properties of the naive repertoire, first after its in...

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Published in:Philosophical transactions of the Royal Society of London. Series B. Biological sciences Vol. 370; no. 1676
Main Authors: Elhanati, Yuval, Sethna, Zachary, Marcou, Quentin, Callan, Jr, Curtis G, Mora, Thierry, Walczak, Aleksandra M
Format: Journal Article
Language:English
Published: England 05.09.2015
Subjects:
Algorithms
Antibody Diversity
B-Lymphocytes - immunology
Clonal Selection, Antigen-Mediated
Humans
Models, Genetic
Models, Immunological
Receptors, Antigen, B-Cell - genetics
Somatic Hypermutation, Immunoglobulin
V(D)J Recombination
B cell
immune repertoire
somatic hypermutations
statistical inference
IgH
VDJ recombination
ISSN:1471-2970
Online Access:Get more information
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Abstract We quantify the VDJ recombination and somatic hypermutation processes in human B cells using probabilistic inference methods on high-throughput DNA sequence repertoires of human B-cell receptor heavy chains. Our analysis captures the statistical properties of the naive repertoire, first after its initial generation via VDJ recombination and then after selection for functionality. We also infer statistical properties of the somatic hypermutation machinery (exclusive of subsequent effects of selection). Our main results are the following: the B-cell repertoire is substantially more diverse than T-cell repertoires, owing to longer junctional insertions; sequences that pass initial selection are distinguished by having a higher probability of being generated in a VDJ recombination event; somatic hypermutations have a non-uniform distribution along the V gene that is well explained by an independent site model for the sequence context around the hypermutation site.
AbstractList We quantify the VDJ recombination and somatic hypermutation processes in human B cells using probabilistic inference methods on high-throughput DNA sequence repertoires of human B-cell receptor heavy chains. Our analysis captures the statistical properties of the naive repertoire, first after its initial generation via VDJ recombination and then after selection for functionality. We also infer statistical properties of the somatic hypermutation machinery (exclusive of subsequent effects of selection). Our main results are the following: the B-cell repertoire is substantially more diverse than T-cell repertoires, owing to longer junctional insertions; sequences that pass initial selection are distinguished by having a higher probability of being generated in a VDJ recombination event; somatic hypermutations have a non-uniform distribution along the V gene that is well explained by an independent site model for the sequence context around the hypermutation site.
Author Walczak, Aleksandra M
Mora, Thierry
Marcou, Quentin
Sethna, Zachary
Elhanati, Yuval
Callan, Jr, Curtis G
Author_xml – sequence: 1
  givenname: Yuval
  surname: Elhanati
  fullname: Elhanati, Yuval
  organization: Laboratoire de physique théorique, UMR8549, CNRS and École normale supérieure, 24, rue Lhomond, 75005 Paris, France
– sequence: 2
  givenname: Zachary
  surname: Sethna
  fullname: Sethna, Zachary
  organization: Joseph Henry Laboratories, Princeton University, Princeton, NJ 08544, USA
– sequence: 3
  givenname: Quentin
  surname: Marcou
  fullname: Marcou, Quentin
  organization: Laboratoire de physique théorique, UMR8549, CNRS and École normale supérieure, 24, rue Lhomond, 75005 Paris, France
– sequence: 4
  givenname: Curtis G
  orcidid: 0000-0001-9937-6160
  surname: Callan, Jr
  fullname: Callan, Jr, Curtis G
  organization: Joseph Henry Laboratories, Princeton University, Princeton, NJ 08544, USA
– sequence: 5
  givenname: Thierry
  surname: Mora
  fullname: Mora, Thierry
  organization: Laboratoire de physique statistique, UMR8550, CNRS and École normale supérieure, 24, rue Lhomond, 75005 Paris, France
– sequence: 6
  givenname: Aleksandra M
  surname: Walczak
  fullname: Walczak, Aleksandra M
  email: awalczak@lpt.ens.fr
  organization: Laboratoire de physique théorique, UMR8549, CNRS and École normale supérieure, 24, rue Lhomond, 75005 Paris, France awalczak@lpt.ens.fr
BackLink https://www.ncbi.nlm.nih.gov/pubmed/26194757$$D View this record in MEDLINE/PubMed
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Keywords B cell
immune repertoire
somatic hypermutations
statistical inference
IgH
VDJ recombination
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Snippet We quantify the VDJ recombination and somatic hypermutation processes in human B cells using probabilistic inference methods on high-throughput DNA sequence...
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SubjectTerms Algorithms
Antibody Diversity
B-Lymphocytes - immunology
Clonal Selection, Antigen-Mediated
Humans
Models, Genetic
Models, Immunological
Receptors, Antigen, B-Cell - genetics
Somatic Hypermutation, Immunoglobulin
V(D)J Recombination
Title Inferring processes underlying B-cell repertoire diversity
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