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Publication : Increased targeting of donor switch region and IgE in Sgamma1-deficient B cells.

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.
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