| First Author | Rouaud P | Year | 2014 |
| Journal | J Exp Med | Volume | 211 |
| Issue | 5 | Pages | 975-85 |
| PubMed ID | 24752300 | Mgi Jnum | J:211306 |
| Mgi Id | MGI:5574420 | Doi | 10.1084/jem.20131385 |
| Citation | Rouaud P, et al. (2014) Elucidation of the enigmatic IgD class-switch recombination via germline deletion of the IgH 3' regulatory region. J Exp Med 211(5):975-85 |
| abstractText | Classical class-switch recombination (cCSR) substitutes the Cmu gene with Cgamma, Cepsilon, or Calpha, 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 mudeltaCSR 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, mudeltaCSR is 3'RR-independent, as its absence affects neither breakpoint locations in Smu- and Sdelta-like (sigma(delta)) nor mutation patterns at Smu-sigma(delta) junctions. Although mutations occur in the immediate proximity of the mudelta junctions, SHM is absent distal to the junctions within both Smu and rearranged VDJ regions. In conclusion, mudeltaCSR 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. |
