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Distinct roles for E12 and E47 in B cell specification and the sequential rearrangement of immunoglobulin light chain loci
The E2A gene products, E12 and E47, are critical regulators of B cell development. However, it remains elusive whether E12 and E47 have overlapping and/or distinct functions during B lymphopoiesis. We have generated mice deficient for either E12 or E47 and examined their roles in B cell maturation....
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2757879/ https://www.ncbi.nlm.nih.gov/pubmed/19752184 http://dx.doi.org/10.1084/jem.20090756 |
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author | Beck, Kristina Peak, Mandy M. Ota, Takayuki Nemazee, David Murre, Cornelis |
author_facet | Beck, Kristina Peak, Mandy M. Ota, Takayuki Nemazee, David Murre, Cornelis |
author_sort | Beck, Kristina |
collection | PubMed |
description | The E2A gene products, E12 and E47, are critical regulators of B cell development. However, it remains elusive whether E12 and E47 have overlapping and/or distinct functions during B lymphopoiesis. We have generated mice deficient for either E12 or E47 and examined their roles in B cell maturation. We show that E47 is essential for developmental progression at the prepro–B cell stage, whereas E12 is dispensable for early B cell development, commitment, and maintenance. In contrast, both E12 and E47 play critical roles in pre–B and immature B cells to promote immunoglobulin λ (Igλ) germline transcription as well as Igλ VJ gene rearrangement. Furthermore, we show that E12 as well as E47 is required to promote receptor editing upon exposure to self-antigen. We demonstrate that increasing levels of E12 and E47 act to induce Igλ germline transcription, promote trimethylated lysine 4 on histone 3 (H3) as well as H3 acetylation across the Jλ region, and activate Igλ VJ gene rearrangement. We propose that in the pre–B and immature B cell compartments, gradients of E12 and E47 activities are established to mechanistically regulate the sequential rearrangement of the Ig light chain genes. |
format | Text |
id | pubmed-2757879 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-27578792010-03-28 Distinct roles for E12 and E47 in B cell specification and the sequential rearrangement of immunoglobulin light chain loci Beck, Kristina Peak, Mandy M. Ota, Takayuki Nemazee, David Murre, Cornelis J Exp Med Article The E2A gene products, E12 and E47, are critical regulators of B cell development. However, it remains elusive whether E12 and E47 have overlapping and/or distinct functions during B lymphopoiesis. We have generated mice deficient for either E12 or E47 and examined their roles in B cell maturation. We show that E47 is essential for developmental progression at the prepro–B cell stage, whereas E12 is dispensable for early B cell development, commitment, and maintenance. In contrast, both E12 and E47 play critical roles in pre–B and immature B cells to promote immunoglobulin λ (Igλ) germline transcription as well as Igλ VJ gene rearrangement. Furthermore, we show that E12 as well as E47 is required to promote receptor editing upon exposure to self-antigen. We demonstrate that increasing levels of E12 and E47 act to induce Igλ germline transcription, promote trimethylated lysine 4 on histone 3 (H3) as well as H3 acetylation across the Jλ region, and activate Igλ VJ gene rearrangement. We propose that in the pre–B and immature B cell compartments, gradients of E12 and E47 activities are established to mechanistically regulate the sequential rearrangement of the Ig light chain genes. The Rockefeller University Press 2009-09-28 /pmc/articles/PMC2757879/ /pubmed/19752184 http://dx.doi.org/10.1084/jem.20090756 Text en © 2009 Beck et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Article Beck, Kristina Peak, Mandy M. Ota, Takayuki Nemazee, David Murre, Cornelis Distinct roles for E12 and E47 in B cell specification and the sequential rearrangement of immunoglobulin light chain loci |
title | Distinct roles for E12 and E47 in B cell specification and the sequential rearrangement of immunoglobulin light chain loci |
title_full | Distinct roles for E12 and E47 in B cell specification and the sequential rearrangement of immunoglobulin light chain loci |
title_fullStr | Distinct roles for E12 and E47 in B cell specification and the sequential rearrangement of immunoglobulin light chain loci |
title_full_unstemmed | Distinct roles for E12 and E47 in B cell specification and the sequential rearrangement of immunoglobulin light chain loci |
title_short | Distinct roles for E12 and E47 in B cell specification and the sequential rearrangement of immunoglobulin light chain loci |
title_sort | distinct roles for e12 and e47 in b cell specification and the sequential rearrangement of immunoglobulin light chain loci |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2757879/ https://www.ncbi.nlm.nih.gov/pubmed/19752184 http://dx.doi.org/10.1084/jem.20090756 |
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