論文 - 詳細
| RRC ID | 27882 |
|---|---|
| 著者 | Pengo N, Scolari M, Oliva L, Milan E, Mainoldi F, Raimondi A, Fagioli C, Merlini A, Mariani E, Pasqualetto E, Orfanelli U, Ponzoni M, Sitia R, Casola S, Cenci S. |
| タイトル | Plasma cells require autophagy for sustainable immunoglobulin production. |
| ジャーナル | Nat Immunol |
| Abstract |
The role of autophagy in plasma cells is unknown. Here we found notable autophagic activity in both differentiating and long-lived plasma cells and investigated its function through the use of mice with conditional deficiency in the essential autophagic molecule Atg5 in B cells. Atg5(-/-) differentiating plasma cells had a larger endoplasmic reticulum (ER) and more ER stress signaling than did their wild-type counterparts, which led to higher expression of the transcriptional repressor Blimp-1 and immunoglobulins and more antibody secretion. The enhanced immunoglobulin synthesis was associated with less intracellular ATP and more death of mutant plasma cells, which identified an unsuspected autophagy-dependent cytoprotective trade-off between immunoglobulin synthesis and viability. In vivo, mice with conditional deficiency in Atg5 in B cells had defective antibody responses, complete selection in the bone marrow for plasma cells that escaped Atg5 deletion and fewer antigen-specific long-lived bone marrow plasma cells than did wild-type mice, despite having normal germinal center responses. Thus, autophagy is specifically required for plasma cell homeostasis and long-lived humoral immunity. |
| 巻・号 | 14(3) |
| ページ | 298-305 |
| 公開日 | 2013-3-1 |
| DOI | 10.1038/ni.2524 |
| PII | ni.2524 |
| PMID | 23354484 |
| MeSH | Adenosine Triphosphate Animals Antibody Formation Autophagy* Autophagy-Related Protein 5 B-Lymphocytes / immunology B-Lymphocytes / metabolism* Bone Marrow Cells / immunology Cell Differentiation Endoplasmic Reticulum / genetics Endoplasmic Reticulum Stress / genetics Germinal Center / immunology Homeostasis Immunoglobulins / biosynthesis* Lymphocyte Activation Mice Mice, Inbred C57BL Mice, Knockout Microtubule-Associated Proteins / deficiency Microtubule-Associated Proteins / genetics* Plasma Cells / cytology Plasma Cells / immunology* Plasma Cells / metabolism Positive Regulatory Domain I-Binding Factor 1 Transcription Factors / biosynthesis |
| IF | 20.479 |
| 引用数 | 209 |
| WOS 分野 | IMMUNOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 5 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRC00806 |