Lyn Signaling To Upregulate GANP Is Critical for the Survival of High-Affinity B Cells in Germinal Centers of Lymphoid Organs
| Autor: | Nobuo Sakaguchi, Masahiro Kitabatake, Toshitada Takemori, Teruo Nakaya, Teppei Toda, Suchada Phimsen, Kazuhiko Kuwahara, Tomohiro Kaji, Takeshi Watanabe |
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| Rok vydání: | 2012 |
| Předmět: |
Cell Survival
Lymphoid Tissue Transgene Immunology B-Lymphocyte Subsets Mice Transgenic Biology medicine.disease_cause Affinity maturation Mice LYN hemic and lymphatic diseases Cell Adhesion medicine Animals Humans Immunology and Allergy Cells Cultured B cell Mice Knockout Mutation Cell growth breakpoint cluster region Nuclear Proteins Germinal center Germinal Center Phosphoproteins Up-Regulation Cell biology Mice Inbred C57BL src-Family Kinases medicine.anatomical_structure Signal Transduction |
| Zdroj: | The Journal of Immunology. 189:3472-3479 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1200649 |
| Popis: | Signals through BCR and costimulatory molecules play essential roles in selecting high-affinity B cells with Ig V-region mutations in the germinal centers (GCs) of peripheral lymphoid organs. Lyn-deficient (lyn−/−) mice show impaired BCR signal triggering for cell proliferation and GC formation, causing hyper-IgM, and display autoimmunity after aging. In this study, we demonstrate that Lyn-mediated signaling to upregulate GANP is essential for the survival of mature GC-like (mGC) B cells with high-affinity type BCR mutations upon Ag immunization. Transgenic ganp expression into lyn−/− mice did not recover the Lyn-deficient phenotype with regard to B cell differentiation, serum Igs, and impaired GC formation in spleens after immunization with nitrophenyl-chicken γ-globulin, but it markedly rescued cell survival of mGC B cells by suppressing DNA damage, thereby increasing the frequency of the Trp33-to-Leu mutation in the IgVH-186.2 region and affinity maturation of nitrophenyl-binding B cells. GANP may play a critical role in Lyn-mediated signaling for the selection of high-affinity B cells in peripheral lymphoid organs. |
| Databáze: | OpenAIRE |
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