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

Andreasson, Ulrika LU orcid ; Flicker, Sabine ; Lindstedt, Malin LU ; Valenta, Rudolf ; Greiff, Lennart LU ; Korsgren, Magnus LU ; Borrebaeck, Carl LU and Ohlin, Mats LU orcid (2006) In Journal of Molecular Biology 362(2). p.212-227
Abstract
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... (More)
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. (Less)
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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
repertoire, antibody, allergy, phage display, B cell
in
Journal of Molecular Biology
volume
362
issue
2
pages
212 - 227
publisher
Elsevier
external identifiers
  • pmid:16905150
  • wos:000240549200005
  • scopus:33747790631
ISSN
1089-8638
DOI
10.1016/j.jmb.2006.06.062
project
Human IgE repertoires and an anti-allergome resource
language
English
LU publication?
yes
id
1d746b8f-6144-4440-bfa4-cb67d9becd0b (old id 393026)
date added to LUP
2016-04-01 15:43:25
date last changed
2022-04-14 23:34:39
@article{1d746b8f-6144-4440-bfa4-cb67d9becd0b,
  abstract     = {{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.}},
  author       = {{Andreasson, Ulrika and Flicker, Sabine and Lindstedt, Malin and Valenta, Rudolf and Greiff, Lennart and Korsgren, Magnus and Borrebaeck, Carl and Ohlin, Mats}},
  issn         = {{1089-8638}},
  keywords     = {{repertoire; antibody; allergy; phage display; B cell}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{212--227}},
  publisher    = {{Elsevier}},
  series       = {{Journal of Molecular Biology}},
  title        = {{The human IgE-encoding transcriptome to assess antibody repertoires and repertoire evolution}},
  url          = {{http://dx.doi.org/10.1016/j.jmb.2006.06.062}},
  doi          = {{10.1016/j.jmb.2006.06.062}},
  volume       = {{362}},
  year         = {{2006}},
}