The IgH 3' regulatory region controls somatic hypermutation in germinal center B cells.
摘要：
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.
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关键词：
Germinal Center B-Lymphocytes Animals Mice, Knockout Mice Cytidine Deaminase Immunoglobulin Variable Region 3' Untranslated Regions Chromatin Immunoprecipitation
DOI：
10.1084/jem.20130072
被引量：
年份：
2013
国家科技图书文献中心
(权威机构)
掌桥科研
Semantic Scholar
万方医学
dx.doi.org
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