Elucidation of the enigmatic IgD class-switch recombination via germline deletion of the IgH 3' regulatory region - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Experimental Medicine Année : 2014

Elucidation of the enigmatic IgD class-switch recombination via germline deletion of the IgH 3' regulatory region

Résumé

Classical class-switch recombination (cCSR) substitutes the Cμ gene with Cγ, Cε, or Cα, thereby generating IgG, IgE, or IgA classes, respectively. This activation-induced deaminase (AID)-driven process is controlled by the IgH 3' regulatory region (3'RR). Regulation of rare IgD CSR events has been enigmatic. We show that μδCSR occurs in mouse mesenteric lymph node (MLN) B cells and is AID-dependent. AID attacks differ from those in cCSR because they are not accompanied by extensive somatic hypermutation (SHM) of targeted regions and because repaired junctions exhibit features of the alternative end-joining (A-EJ) pathway. In contrast to cCSR and SHM, μδCSR is 3'RR-independent, as its absence affects neither breakpoint locations in Sμ- and Sδ-like (σ(δ)) nor mutation patterns at Sμ-σ(δ) junctions. Although mutations occur in the immediate proximity of the μδ junctions, SHM is absent distal to the junctions within both Sμ and rearranged VDJ regions. In conclusion, μδCSR is active in MLNs, occurs independently of 3'RR-driven assembly, and is even dramatically increased in 3'RR-deficient mice, further showing that its regulation differs from cCSR.

Domaines

Immunologie
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Dates et versions

hal-01212566 , version 1 (06-10-2015)

Identifiants

  • HAL Id : hal-01212566 , version 1
  • PUBMED : 24752300

Citer

Pauline Rouaud, Alexis Saintamand, Faten Saad, Claire Carrion, Sandrine Lecardeur, et al.. Elucidation of the enigmatic IgD class-switch recombination via germline deletion of the IgH 3' regulatory region. Journal of Experimental Medicine, 2014. ⟨hal-01212566⟩
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