The analysis of clonal expansions in normal and autoimmune B cell repertoires

Uri Hershberg, Eline T. Luning Prak

Research output: Contribution to journalReview articlepeer-review


Clones are the fundamental building blocks of immune repertoires. The number of different clones relates to the diversity of the repertoire, whereas their size and sequence diversity are linked to selective pressures. Selective pressures act both between clones and within different sequence variants of a clone. Understanding how clonal selection shapes the immune repertoire is one of the most basic questions in all of immunology. But howare individual clones defined? Here we discuss different approaches for defining clones, starting with how antibodies are diversified during different stages of B cell development. Next, we discuss how clones are defined using different experimental methods. We focus on high-throughput sequencing datasets, and the computational challenges and opportunities that these data have for mining the antibody repertoire landscape. We discuss methods that visualize sequence variants within the same clone and allowus to consider collections of shared mutations to determine which sequences share a common ancestry. Finally, we comment on features of frequently encountered expanded B cell clones that may be of particular interest in the setting of autoimmunity and other chronic conditions.

Original languageEnglish
JournalPhilosophical Transactions of the Royal Society B: Biological Sciences
Issue number1676
StatePublished - 5 Sep 2015
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2015 The Author(s) Published by the Royal Society. All rights reserved.


  • Antibody
  • Clone
  • Clonotype
  • High-throughput sequencing
  • Immunoglobulin
  • Repertoire

ASJC Scopus subject areas

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


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