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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 賈景山(Jean-San Chia) | |
| dc.contributor.author | Yu-Rou Lan | en |
| dc.contributor.author | 藍語柔 | zh_TW |
| dc.date.accessioned | 2021-06-17T01:16:22Z | - |
| dc.date.available | 2022-08-14 | |
| dc.date.copyright | 2017-09-13 | |
| dc.date.issued | 2017 | |
| dc.date.submitted | 2017-08-14 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/66984 | - |
| dc.description.abstract | 細菌和病毒的感染可能會使宿主產生自體免疫疾病，在感染性心內膜炎的患者體內，也可以發現許多自體抗體生成。我們先前的研究發現，若將人類口腔中常見的轉糖鏈球菌 (Streptococcus mutans) 從尾靜脈感染老鼠，則老鼠在五天內就會產生抗雙股去氧核醣核酸抗體 (anti-dsDNA antibody)，但其中的機制目前尚不清楚。我們從受感染的老鼠血清中純化出抗雙股去氧核醣核酸抗體，並且發現這些抗體可以專一性辨認轉糖鏈球菌的表面蛋白葡糖基轉移酶 B (glucosyltransferase B, GtfB)。從尾靜脈注射GtfB重組蛋白至老鼠體內，同樣可以使老鼠產生抗雙股去氧核醣核酸抗體，表示GtfB在產生抗雙股去氧核醣核酸抗體扮演一定的角色。GtfB可以結合至轉糖鏈球菌的染色體，但無法結合至小牛胸線之去氧核醣核酸 (calf thymus DNA)。為了研究抗體產生的機制，我們也將轉糖鏈球菌和GtfB從尾靜脈打入邊緣區B細胞缺失 (marginal zone B cell knockout) 的老鼠體內，發現牠們無法產生抗雙股去氧核醣核酸抗體，表示邊緣區B細胞扮演重要角色。以上結果顯示，血液循環中的GtfB可以結合細菌之去氧核醣核酸，進而刺激邊緣區B細胞產生抗雙股去氧核醣核酸抗體。 | zh_TW |
| dc.description.abstract | Infections play roles in the development of autoimmune diseases. Our previous data showed that bacteremia caused by Streptococcus mutans, an oral commensal, induces autoantibody production within five days, but the mechanism remains unclear. Here, we purified the anti-dsDNA antibodies isolated from mice with Streptococcus mutans bacteremia, and identified a bacterial surface protein, glucosyltransferase B (GtfB), that can specifically be recognized by the anti-dsDNA antibodies. Intravascularly injection of recombinant GtfB induces anti-dsDNA antibody production in C57BL/6 mice, confirming the role of GtfB. GtfB can specifically bind to S. mutans genomic DNA, not calf thymus DNA, in a dose-dependent manner. Intravascularly injection of S. mutans or recombinant GtfB failed to induce the anti-dsDNA antibody production in marginal zone B cell knockout mice, suggesting the role of marginal zone B cells. Taken together, our data suggested GtfB stimulates marginal zone B cells to produce anti-dsDNA antibody through binding with bacterial DNA. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-17T01:16:22Z (GMT). No. of bitstreams: 1 ntu-106-R04449009-1.pdf: 1353555 bytes, checksum: d227b832bb1d5c1b83a31a6823464d3c (MD5) Previous issue date: 2017 | en |
| dc.description.tableofcontents | 口試委員會審定書 I
致謝 II Abstract III 中文摘要 IV Contents V 表目錄 VIII 圖目錄 IX Chapter 1. Introduction 1 1.1 Streptococcus mutans 1 1.2 Glucosyltransferase 1 1.3 Spleen 2 1.4 Marginal zone B cell (MZ B) 3 1.5 Autoantibody production 4 1.6 Antibody isotypes and subclasses 5 Chapter 2.Purpose and Specific Aim 7 Chapter 3. Materials and methods 8 3.1 Animals 8 3.2 Splenectomy procedures 8 3.3 Bacterial strains and growth conditions 9 3.4 Streptococcal cell wall-associated (CA) proteins extraction 9 3.5 Construction of His-tagged GtfB in S. mutans 10 3.6 Chromosomal integration of His-tagged GtfB in S. mutans 11 3.7 Recombinant protein expression and purification 12 3.8 Extraction of S. mutans genomic DNA 12 3.9 Enzyme-linked immunosorbent assay (ELISA) 13 3.10 DNA-binding activity assay 14 3.11 Antibody elution from ELISA plate wells 15 3.12 Anti-dsDNA antibody purification from SLE sera 15 3.13 DNA-binding protein purification from S. mutans CA protein 16 3.14 Western blotting (WB) 16 3.15 Statistical analysis 17 Chapter 4. Results 18 4.1 Spleen plays a role in anti-bacteria and anti-dsDNA IgG production in bacteremia mouse model 18 4.2 Spleen plays a critical role in the production of distinct antibody subtypes against circulating bacteria 18 4.3 Marginal zone B cells play a crucial role in anti-dsDNA antibody production 19 4.4 Eluted anti-dsDNA antibody recognizes S. mutans GtfB 20 4.5 GtfB induces anti-dsDNA antibody production in a MZ B-dependent manner. 21 4.6 DNA-binding ability of GtfB 21 Chapter 5. Discussion 23 5.1 Bacterial protein GtfB is important for anti-dsDNA antibody production 23 5.2 The DNA-binding activity of GtfB 23 5.3 The difference between eukaryotic DNA and bacterial DNA 24 5.4 GtfB may activate MZ B cells through TLR9 signaling 24 Chapter 6. References 26 Chapter 7. Table 33 Chapter 8. Figures 34 | |
| dc.language.iso | en | |
| dc.title | 探討血液循環系統中轉糖鏈球菌之葡糖基轉移酶B引發抗雙股去氧核糖核酸抗體生成之機制 | zh_TW |
| dc.title | Mechanism of Anti-dsDNA Antibody Production Induced by Circulating Streptococcus mutans GtfB | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 105-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 鍾筱菁(Chiau-Jing Jung),顧家綺(Chia-Chi Ku) | |
| dc.subject.keyword | 轉糖鏈球菌,葡糖基轉移?Ｂ,抗雙股去氧核醣核酸抗體,邊緣區Ｂ細胞,細菌雙股去氧核醣核酸, | zh_TW |
| dc.subject.keyword | Streptococcus mutans,glucosyltransferase B,anti-dsDNA antibody,marginal zone B cell,bacterial DNA, | en |
| dc.relation.page | 45 | |
| dc.identifier.doi | 10.6342/NTU201703053 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2017-08-14 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 免疫學研究所 | zh_TW |
| 顯示於系所單位： | 免疫學研究所 | |
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