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

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.

journal_name

J Mol Biol

journal_title

Journal of molecular biology

authors

Andréasson U,Flicker S,Lindstedt M,Valenta R,Greiff L,Korsgren M,Borrebaeck CA,Ohlin M

doi

10.1016/j.jmb.2006.06.062

subject

Has Abstract

pub_date

2006-09-15 00:00:00

pages

212-27

issue

2

eissn

0022-2836

issn

1089-8638

pii

S0022-2836(06)00706-6

journal_volume

362

pub_type

杂志文章

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