| First Author | Misaghi S | Year | 2010 |
| Journal | J Immunol | Volume | 185 |
| Issue | 1 | Pages | 166-73 |
| PubMed ID | 20511552 | Mgi Jnum | J:161437 |
| Mgi Id | MGI:4459329 | Doi | 10.4049/jimmunol.1000515 |
| Citation | Misaghi S, et al. (2010) Increased targeting of donor switch region and IgE in Sgamma1-deficient B cells. J Immunol 185(1):166-73 |
| abstractText | Ab class switch recombination involves a recombination between two repetitive DNA sequences known as switch (S) regions that vary in length, content, and density of the repeats. Abs expressed by B cells are diversified by somatic hypermutation and class switch recombination. Both class switch recombination and somatic hypermutation are initiated by activation-induced cytidine deaminase (AID), which preferentially recognizes certain hot spots that are far more enriched in the S regions. We found that removal of the largest S region, Sgamma1 (10 kb), in mice can result in the accumulation of mutations and short-range intra-S recombination in the donor Smu region. Furthermore, elevated levels of IgE were detected in trinitrophenol-OVA-immunized mice and in anti-CD40 plus IL-4-stimulated B cells in vitro. We propose that AID availability and targeting in part might be regulated by its DNA substrate. Thus, prominently transcribed S regions, such as Sgamma1, might provide a sufficient sink for AID protein to titrate away AID from other accessible sites within or outside the Ig locus. |