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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Bach, Martina P. Maruya, Mikako Fagarasan, Sidonia Kishigami, Satoshi Wakayama, Teruhiko Casola, Stefano Jumaa, Hassan Kanagawa, Osami Kumar, Rashmi Mainoldi, Federica |
| Description | Author Affiliation: Kumar R ( The Institute of Molecular Oncology (IFOM) of the Italian Foundation for Cancer Research (FIRC), Milan 20139, Italy); Bach MP ( Institute of Immunology, University Clinic Ulm, 89081 Ulm, Germany); Mainoldi F ( The Institute of Molecular Oncology (IFOM) of the Italian Foundation for Cancer Research (FIRC), Milan 20139, Italy); Maruya M ( Center for Integrative Medical Sciences, RIKEN Yokohama Institute, Yokohama, Kanagawa 230-0045, Japan); Kishigami S ( RIKEN Center for Developmental Biology, Kobe, Hyogo 650-0047, Japan); Jumaa H ( Institute of Immunology, University Clinic Ulm, 89081 Ulm, Germany); Wakayama T ( RIKEN Center for Developmental Biology, Kobe, Hyogo 650-0047, Japan); Kanagawa O ( Akashi City Hospital, Akashi 673-8501, Japan.); Fagarasan S ( Center for Integrative Medical Sciences, RIKEN Yokohama Institute, Yokohama, Kanagawa 230-0045, Japan); Casola S ( The Institute of Molecular Oncology (IFOM) of the Italian Foundation for Cancer Research (FIRC), Milan 20139, Italy); |
| Abstract | In mammals, VDJ recombination is responsible for the establishment of a highly diversified preimmune antibody repertoire. Acquisition of a functional Ig heavy (H) chain variable (V) gene rearrangement is thought to prevent further recombination at the IgH locus. Here, we describe VHQ52(NT); Vκgr32(NT) Ig monoclonal mice reprogrammed from the nucleus of an intestinal IgA(+) plasma cell. In VHQ52(NT) mice, IgA replaced IgM to drive early B-cell development and peripheral B-cell maturation. In VHQ52(NT) animals, over 20% of mature B cells disrupted the single productive, nonautoimmune IgH rearrangement through VH replacement and exchanged it with a highly diversified pool of IgH specificities. VH replacement occurred in early pro-B cells, was independent of pre-B-cell receptor signaling, and involved predominantly one adjacent VH germ-line gene. VH replacement was also identified in 5% of peripheral B cells of mice inheriting a different productive VH rearrangement expressed in the form of an IgM H chain. In summary, editing of a productive IgH rearrangement through VH replacement can account for up to 20% of the IgH repertoire expressed by mature B cells. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 5 |
| Volume Number | 112 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2015-02-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Cloning, Organism Immunoglobulin A Immunology Immunoglobulin Heavy Chains Genetics Immunoglobulin Variable Region Animals Mice Molecular Sequence Data Sequence Homology, Nucleic Acid Signal Transduction Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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