Inferring processes underlying B-cell repertoire diversity

Yuval Elhanati, Zachary Sethna, Quentin Marcou, Curtis G. Callan, Thierry Mora, Aleksandra M. Walczak

Research output: Contribution to journalArticle

68 Scopus citations

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).Ourmain 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 aVDJ recombination event; somatic hypermutations have a non-uniformdistribution along the V gene that iswell explained by an independent site model for the sequence context around the hypermutation site.

Original languageEnglish (US)
JournalPhilosophical Transactions of the Royal Society B: Biological Sciences
Volume370
Issue number1676
DOIs
StatePublished - Sep 5 2015

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Keywords

  • B cell
  • IgH
  • Immune repertoire
  • Somatic hypermutations
  • Statistical inference
  • VDJ recombination

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