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Philos Trans R Soc Lond B Biol Sci. 2015 Sep 5;370(1676). pii: 20140239. doi: 10.1098/rstb.2014.0239.

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

Author information

1
School of Biomedical Engineering, Science and Health Systems, Drexel University, Bossone 7-711, 3141 Chestnut Street, Philadelphia, PA 19104, USA Department of Immunology and Microbiology, College of Medicine, Drexel University, Bossone 7-711, 3141 Chestnut Street, Philadelphia, PA 19104, USA.
2
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, 405B Stellar Chance Labs, 422 Curie Boulevard, Philadelphia, PA 19104, USA luning@mail.med.upenn.edu.

Abstract

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 how are 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 allow us 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.

KEYWORDS:

antibody; clone; clonotype; high-throughput sequencing; immunoglobulin; repertoire

PMID:
26194753
PMCID:
PMC4528416
DOI:
10.1098/rstb.2014.0239
[Indexed for MEDLINE]
Free PMC Article

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