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

Date publication

juillet 2013

Auteurs

Membres identifiés du Cancéropôle Est :
Dr REINA-SAN-MARTIN Bernardo

Tous les auteurs :
Rouaud P, Vincent-Fabert C, Saintamand A, Fiancette R, Marquet M, Robert I, Reina-San-Martin B, Pinaud E, Cogne M, Denizot Y

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/23825188

Résumé

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 Emu enhancer upstream of Cmu 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 kappa 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.

Référence

J Exp Med. 2013 Jul 29;210(8):1501-7