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The human IgE-encoding transcriptome to assess antibody repertoires and repertoire evolution

Author:
  • Ulrika Andreasson
  • Sabine Flicker
  • Malin Lindstedt
  • Rudolf Valenta
  • Lennart Greiff
  • Magnus Korsgren
  • Carl Borrebaeck
  • Mats Ohlin
Publishing year: 2006
Language: English
Pages: 212-227
Publication/Series: Journal of Molecular Biology
Volume: 362
Issue: 2
Document type: Journal article
Publisher: Elsevier

Abstract english

Upon encounter with antigen, the B lymphocyte population responds by producing a diverse set of antigen-specific antibodies of various isotypes. The vast size of the responding populations makes it very difficult to study clonal evolution and repertoire composition occurring during these processes in humans. Here, we have explored an approach utilizing the H-EPSILON-encoding transcriptome to investigate aspects of repertoire diversity during the season of antigen exposure. We show through sequencing of randomly picked transcripts that the sizes of patients' repertoires are relatively small. This specific aspect of the transcriptome allows us to construct evolutionary trees pinpointing features of somatic hypermutation as it occurs in humans. Despite the small size of the repertoires, they are highly diverse with respect to VDJ gene usage, suggesting that the H-EPSILON-encoding transcriptome is a faithful mimic of other class-switched isotypes. Importantly, it is possible to use antibody library and selection technologies to define the specificity of clonotypes identified by random sequencing. The small size of the H-EPSILON-encoding transcriptome of peripheral blood B cells, the simple identification of clonally related sets of genes in this population, and the power of library and selection technologies ensure that this approach will allow us to investigate antibody evolution in human B lymphocytes of known specificity. As H-EPSILON repertoires show many of the hallmarks of repertoires encoding other isotypes, we suggest that studies of this type will have an impact on our understanding of human antibody evolution even beyond that occurring in the IgE-producing B cell population.

Keywords

  • Medicinal Chemistry
  • Pharmacology and Toxicology
  • repertoire
  • antibody
  • allergy
  • phage display
  • B cell

Other

Published
  • ISSN: 1089-8638
Carl Borrebaeck
E-mail: carl [dot] borrebaeck [at] immun [dot] lth [dot] se

Professor

Department of Immunotechnology

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