Polyclonal hyper-IgE mouse model reveals mechanistic insights into antibody class switch recombination
| العنوان: | Polyclonal hyper-IgE mouse model reveals mechanistic insights into antibody class switch recombination |
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| المؤلفون: | Mercedesz Balazs, Donghong Yan, Maria N. Lorenzo, Tao Sai, Laura DeForge, Kajal Hamidzadeh, Andrew Sebrell, Yan Qu, Jin Zhaoyu, Merone Roose-Girma, Meijuan Zhou, Patrick Caplazi, Wyne P. Lee, Min Xu, Yonglian Sun, Zhonghua Lin, Kate Senger, Wei Yu Lin, Jiabing Ding, Shahram Misaghi, Allen Nguyen, Ali A. Zarrin, Søren Warming, Cary D. Austin, Vishva M. Dixit |
| المصدر: | Proceedings of the National Academy of Sciences. 110:15770-15775 |
| بيانات النشر: | Proceedings of the National Academy of Sciences, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Recombination hotspot, Lymphocyte Activation, Immunoglobulin E, Mice, Activation-induced (cytidine) deaminase, Animals, Gene Knock-In Techniques, RNA, Messenger, Alleles, Recombination, Genetic, Genetics, B-Lymphocytes, Hybridomas, Multidisciplinary, biology, Immunoglobulin mu-Chains, Gene targeting, Cytidine deaminase, Biological Sciences, Immunoglobulin Class Switching, Germ Cells, Immunoglobulin class switching, Genetic Loci, Gene Targeting, Models, Animal, biology.protein, Immunoglobulin epsilon-Chains, Antibody, Recombination |
| الوصف: | Preceding antibody constant regions are switch (S) regions varying in length and repeat density that are targets of activation-induced cytidine deaminase. We asked how participating S regions influence each other to orchestrate rearrangements at the IgH locus by engineering mice in which the weakest S region, Sε, is replaced with prominent recombination hotspot Sμ. These mice produce copious polyclonal IgE upon challenge, providing a platform to study IgE biology and therapeutic interventions. The insertion enhances ε germ-line transcript levels, shows a preference for direct vs. sequential switching, and reduces intraswitch recombination events at native Sμ. These results suggest that the sufficiency of Sμ to mediate IgH rearrangements may be influenced by context-dependent cues. |
| تدمد: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1221661110 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bba4e540cf59a6dd15e59e52d423e521 https://doi.org/10.1073/pnas.1221661110 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....bba4e540cf59a6dd15e59e52d423e521 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10916490 00278424 |
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| DOI: | 10.1073/pnas.1221661110 |