High resolution analysis of the chromatin landscape of the IgE switch region in human B cells.

Antibodies are assembled by a highly orchestrated series of recombination events during B cell development. One of these events, class switch recombination, is required to produce the IgG, IgE and IgA antibody isotypes characteristic of a secondary immune response. The action of the enzyme activatio...

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Main Authors: Sandeep Dayal, Jakub Nedbal, Philip Hobson, Alison M Cooper, Hannah J Gould, Martin Gellert, Gary Felsenfeld, David J Fear
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0024571&type=printable
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author Sandeep Dayal
Jakub Nedbal
Philip Hobson
Alison M Cooper
Hannah J Gould
Martin Gellert
Gary Felsenfeld
David J Fear
author_facet Sandeep Dayal
Jakub Nedbal
Philip Hobson
Alison M Cooper
Hannah J Gould
Martin Gellert
Gary Felsenfeld
David J Fear
author_sort Sandeep Dayal
collection DOAJ
description Antibodies are assembled by a highly orchestrated series of recombination events during B cell development. One of these events, class switch recombination, is required to produce the IgG, IgE and IgA antibody isotypes characteristic of a secondary immune response. The action of the enzyme activation induced cytidine deaminase is now known to be essential for the initiation of this recombination event. Previous studies have demonstrated that the immunoglobulin switch regions acquire distinct histone modifications prior to recombination. We now present a high resolution analysis of these histone modifications across the IgE switch region prior to the initiation of class switch recombination in primary human B cells and the human CL-01 B cell line. These data show that upon stimulation with IL-4 and an anti-CD40 antibody that mimics T cell help, the nucleosomes of the switch regions are highly modified on histone H3, accumulating acetylation marks and tri-methylation of lysine 4. Distinct peaks of modified histones are found across the switch region, most notably at the 5' splice donor site of the germline (I) exon, which also accumulates AID. These data suggest that acetylation and K4 tri-methylation of histone H3 may represent marks of recombinationally active chromatin and further implicates splicing in the regulation of AID action.
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spelling doaj-art-fcfbb95a08de43cea8d5df8eb6b5a4dd2025-08-20T03:25:11ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0169e2457110.1371/journal.pone.0024571High resolution analysis of the chromatin landscape of the IgE switch region in human B cells.Sandeep DayalJakub NedbalPhilip HobsonAlison M CooperHannah J GouldMartin GellertGary FelsenfeldDavid J FearAntibodies are assembled by a highly orchestrated series of recombination events during B cell development. One of these events, class switch recombination, is required to produce the IgG, IgE and IgA antibody isotypes characteristic of a secondary immune response. The action of the enzyme activation induced cytidine deaminase is now known to be essential for the initiation of this recombination event. Previous studies have demonstrated that the immunoglobulin switch regions acquire distinct histone modifications prior to recombination. We now present a high resolution analysis of these histone modifications across the IgE switch region prior to the initiation of class switch recombination in primary human B cells and the human CL-01 B cell line. These data show that upon stimulation with IL-4 and an anti-CD40 antibody that mimics T cell help, the nucleosomes of the switch regions are highly modified on histone H3, accumulating acetylation marks and tri-methylation of lysine 4. Distinct peaks of modified histones are found across the switch region, most notably at the 5' splice donor site of the germline (I) exon, which also accumulates AID. These data suggest that acetylation and K4 tri-methylation of histone H3 may represent marks of recombinationally active chromatin and further implicates splicing in the regulation of AID action.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0024571&type=printable
spellingShingle Sandeep Dayal
Jakub Nedbal
Philip Hobson
Alison M Cooper
Hannah J Gould
Martin Gellert
Gary Felsenfeld
David J Fear
High resolution analysis of the chromatin landscape of the IgE switch region in human B cells.
PLoS ONE
title High resolution analysis of the chromatin landscape of the IgE switch region in human B cells.
title_full High resolution analysis of the chromatin landscape of the IgE switch region in human B cells.
title_fullStr High resolution analysis of the chromatin landscape of the IgE switch region in human B cells.
title_full_unstemmed High resolution analysis of the chromatin landscape of the IgE switch region in human B cells.
title_short High resolution analysis of the chromatin landscape of the IgE switch region in human B cells.
title_sort high resolution analysis of the chromatin landscape of the ige switch region in human b cells
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0024571&type=printable
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