The IgH 3' regulatory region controls somatic hypermutation in germinal center B cells

Interactions with cognate antigens recruit activated B cells into germinal centers where they undergo somatic hypermutation (SHM) in V(D)J exons for the generation of high-affinity antibodies. The contribution of IgH transcriptional enhancers in SHM is unclear. The Eμ enhancer upstream of Cμ has a m...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of experimental medicine 2013-07, Vol.210 (8), p.1501-1507
Main Authors: Rouaud, Pauline, Vincent-Fabert, Christelle, Saintamand, Alexis, Fiancette, Rémi, Marquet, Marie, Robert, Isabelle, Reina-San-Martin, Bernardo, Pinaud, Eric, Cogné, Michel, Denizot, Yves
Format: Article
Language:English
Subjects:
3' Untranslated Regions
Animals
B-Lymphocytes
B-Lymphocytes - immunology
B-Lymphocytes - metabolism
Brief Definitive Report
Chromatin Immunoprecipitation
Cytidine Deaminase
Cytidine Deaminase - genetics
Cytidine Deaminase - metabolism
Gene Expression
Gene Expression Regulation
Germinal Center
Germinal Center - cytology
Germinal Center - immunology
Immunoglobulin Heavy Chains
Immunoglobulin Heavy Chains - genetics
Immunoglobulin kappa-Chains
Immunoglobulin kappa-Chains - genetics
Immunoglobulin Variable Region
Immunoglobulin Variable Region - genetics
Immunology
Life Sciences
Mice
Mice, Knockout
Regulatory Sequences, Nucleic Acid
Somatic Hypermutation, Immunoglobulin
Transcription, Genetic
VDJ Exons
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Interactions with cognate antigens recruit activated B cells into germinal centers where they undergo somatic hypermutation (SHM) in V(D)J exons for the generation of high-affinity antibodies. The contribution of IgH transcriptional enhancers in SHM is unclear. The Eμ enhancer upstream of Cμ has a marginal role, whereas the influence of the IgH 3' regulatory region (3'RR) enhancers (hs3a, hs1,2, hs3b, and hs4) is controversial. To clarify the latter issue, we analyzed mice lacking the whole 30-kb extent of the IgH 3'RR. We show that SHM in VH rearranged regions is almost totally abrogated in 3'RR-deficient mice, whereas the simultaneous Ig heavy chain transcription rate is only partially reduced. In contrast, SHM in κ light chain genes remains unaltered, acquitting for any global SHM defect in our model. Beyond class switch recombination, the IgH 3'RR is a central element that controls heavy chain accessibility to activation-induced deaminase modifications including SHM.
ISSN:0022-1007
1540-9538
DOI:10.1084/jem.20130072