miR-29 Sustains B Cell Survival and Controls Terminal Differentiation via Regulation of PI3K Signaling
| Autor: | Eric J. Wigton, Victoria Osorio-Vasquez, Cosmin Tegla, Oriana A. Perez, Marcus J. Hines, Tenny Mudianto, K. Mark Ansel, Maryaline Coffre, Robin Kageyama, David Benhamou, Marisella Panduro, Michael T. McManus, Sergei B. Koralov, Sofia Bajwa, Doron Melamed |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
PTEN miR-29 B-cell receptor Medical Physiology Terminal Differentiation Plasma cell PI3K General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Mice Phosphatidylinositol 3-Kinases 0302 clinical medicine Class Switch Recombination Plasma cell differentiation medicine Genetics Tensin Animals Humans lcsh:QH301-705.5 CSR PI3K/AKT/mTOR pathway B cell miRNA B-Lymphocytes biology B lymphocyte Cell Differentiation Survival Analysis Cell biology MicroRNAs 030104 developmental biology medicine.anatomical_structure lcsh:Biology (General) Immunoglobulin class switching biology.protein Plasma Cell Biochemistry and Cell Biology 030217 neurology & neurosurgery Signal Transduction Biotechnology |
| Zdroj: | Cell reports, vol 33, iss 9 Cell Rep Cell Reports, Vol 33, Iss 9, Pp 108436-(2020) |
| Popis: | Summary: The phosphatidylinositol 3-kinase (PI3K) signaling cascade downstream of the B cell receptor (BCR) signalosome is essential for B cell maturation. Proper signaling strength is maintained through the PI3K negative regulator phosphatase and tensin homolog (PTEN). Although a role for microRNA (miRNA)-dependent control of the PTEN-PI3K axis has been described, the contribution of individual miRNAs to the regulation of this crucial signaling modality in mature B lymphocytes remains to be elucidated. Our analyses reveal that ablation of miR-29 specifically in B lymphocytes results in an increase in PTEN expression and dampening of the PI3K pathway in mature B cells. This dysregulation has a profound impact on the survival of B lymphocytes and results in increased class switch recombination and decreased plasma cell differentiation. Furthermore, we demonstrate that ablation of one copy of Pten is sufficient to ameliorate the phenotypes associated with miR-29 loss. Our data suggest a critical role for the miR-29-PTEN-PI3K regulatory axis in mature B lymphocytes. |
| Databáze: | OpenAIRE |
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