Increased Targeting of Donor Switch Region and IgE in Sγ1-Deficient B Cells
| Autor: | Juan Zhang, Wyne P. Lee, Vishva M. Dixit, Kate Senger, Allen Nguyen, Donghong Yan, Maria N. Lorenzo, Yonglian Sun, Shahram Misaghi, Sherry Heldens, Ali A. Zarrin, Tao Sai, Christopher Garris, Jiansheng Wu, Laura DeForge, Andrew Sebrell, Min Xu |
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| Rok vydání: | 2010 |
| Předmět: |
Immunology
B-Lymphocyte Subsets Somatic hypermutation Immunoglobulin E Mice chemistry.chemical_compound Animals Humans Immunology and Allergy Repeated sequence Cells Cultured Recombination Genetic biology Cytidine deaminase Immunoglobulin Class Switching Molecular biology Mice Mutant Strains Immunoglobulin Switch Region Immunoglobulin Isotypes Mice Inbred C57BL Immunoglobulin class switching chemistry Gene Targeting biology.protein Somatic Hypermutation Immunoglobulin Antibody Gene Deletion Recombination DNA |
| Zdroj: | The Journal of Immunology. 185:166-173 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1000515 |
| Popis: | 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, Sγ1 (10 kb), in mice can result in the accumulation of mutations and short-range intra-S recombination in the donor Sμ 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 Sγ1, might provide a sufficient sink for AID protein to titrate away AID from other accessible sites within or outside the Ig locus. |
| Databáze: | OpenAIRE |
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