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J Exp Med. 2013 Jul 29;210(8):1501-7. doi: 10.1084/jem.20130072. Epub 2013 Jul 1.

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

Author information

1
Centre National de la Recherche Scientifique (CNRS) UMR 7276, Université de Limoges, 87025 Limoges, France.

Abstract

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.

PMID:
23825188
PMCID:
PMC3727322
DOI:
10.1084/jem.20130072
[Indexed for MEDLINE]
Free PMC Article

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