• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

RNA相关自身抗原通过B细胞抗原受体/Toll样受体7联合激活B细胞。

RNA-associated autoantigens activate B cells by combined B cell antigen receptor/Toll-like receptor 7 engagement.

作者信息

Lau Christina M, Broughton Courtney, Tabor Abigail S, Akira Shizuo, Flavell Richard A, Mamula Mark J, Christensen Sean R, Shlomchik Mark J, Viglianti Gregory A, Rifkin Ian R, Marshak-Rothstein Ann

机构信息

Department of Microbiology, Boston University School of Medicine, MA 02118, USA.

出版信息

J Exp Med. 2005 Nov 7;202(9):1171-7. doi: 10.1084/jem.20050630. Epub 2005 Oct 31.

DOI:10.1084/jem.20050630
PMID:16260486
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2213226/
Abstract

Previous studies (Leadbetter, E.A., I.R. Rifkin, A.H. Hohlbaum, B. Beaudette, M.J. Shlomchik, and A. Marshak-Rothstein. 2002. Nature. 416:603-607; Viglianti, G.A., C.M. Lau, T.M. Hanley, B.A. Miko, M.J. Shlomchik, and A. Marshak-Rothstein. 2003. Immunity. 19:837-847) established the unique capacity of DNA and DNA-associated autoantigens to activate autoreactive B cells via sequential engagement of the B cell antigen receptor (BCR) and Toll-like receptor (TLR) 9. We demonstrate that this two-receptor paradigm can be extended to the BCR/TLR7 activation of autoreactive B cells by RNA and RNA-associated autoantigens. These data implicate TLR recognition of endogenous ligands in the response to both DNA- and RNA-associated autoantigens. Importantly, the response to RNA-associated autoantigens was markedly enhanced by IFN-alpha, a cytokine strongly linked to disease progression in patients with systemic lupus erythematosus (SLE). As further evidence that TLRs play a key role in autoantibody responses in SLE, we found that autoimmune-prone mice, lacking the TLR adaptor protein MyD88, had markedly reduced chromatin, Sm, and rheumatoid factor autoantibody titers.

摘要

先前的研究（Leadbetter, E.A., I.R. Rifkin, A.H. Hohlbaum, B. Beaudette, M.J. Shlomchik, and A. Marshak-Rothstein. 2002. 《自然》. 416:603 - 607；Viglianti, G.A., C.M. Lau, T.M. Hanley, B.A. Miko, M.J. Shlomchik, and A. Marshak-Rothstein. 2003. 《免疫》. 19:837 - 847）证实，DNA及与DNA相关的自身抗原具有独特能力，可通过B细胞抗原受体（BCR）和Toll样受体（TLR）9的顺序结合来激活自身反应性B细胞。我们证明，这种双受体模式可扩展至RNA及与RNA相关的自身抗原对自身反应性B细胞的BCR/TLR7激活。这些数据表明，在对与DNA和RNA相关的自身抗原的反应中，内源性配体可被TLR识别。重要的是，α干扰素可显著增强对与RNA相关的自身抗原的反应，α干扰素是一种与系统性红斑狼疮（SLE）患者疾病进展密切相关的细胞因子。作为TLR在SLE自身抗体反应中起关键作用的进一步证据，我们发现缺乏TLR衔接蛋白MyD88的自身免疫易感小鼠，其染色质、Sm和类风湿因子自身抗体滴度显著降低。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9453/2213226/c0e45b2ee8f4/20050630f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9453/2213226/045016bab60b/20050630f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9453/2213226/e9a2eb027960/20050630f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9453/2213226/f735e352c94c/20050630f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9453/2213226/c0e45b2ee8f4/20050630f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9453/2213226/045016bab60b/20050630f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9453/2213226/e9a2eb027960/20050630f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9453/2213226/f735e352c94c/20050630f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9453/2213226/c0e45b2ee8f4/20050630f4.jpg

相似文献

1
RNA-associated autoantigens activate B cells by combined B cell antigen receptor/Toll-like receptor 7 engagement.RNA相关自身抗原通过B细胞抗原受体/Toll样受体7联合激活B细胞。
J Exp Med. 2005 Nov 7;202(9):1171-7. doi: 10.1084/jem.20050630. Epub 2005 Oct 31.
2
Cell-intrinsic expression of TLR9 in autoreactive B cells constrains BCR/TLR7-dependent responses.自身反应性B细胞中TLR9的细胞内源性表达限制了BCR/TLR7依赖性反应。
J Immunol. 2015 Mar 15;194(6):2504-12. doi: 10.4049/jimmunol.1402425. Epub 2015 Feb 13.
3
Toll-like receptor 7 and TLR9 dictate autoantibody specificity and have opposing inflammatory and regulatory roles in a murine model of lupus.Toll样受体7和TLR9决定自身抗体特异性，并在狼疮小鼠模型中具有相反的炎症和调节作用。
Immunity. 2006 Sep;25(3):417-28. doi: 10.1016/j.immuni.2006.07.013.
4
DNA-like class R inhibitory oligonucleotides (INH-ODNs) preferentially block autoantigen-induced B-cell and dendritic cell activation in vitro and autoantibody production in lupus-prone MRL-Fas(lpr/lpr) mice in vivo.类 DNA 抑制性寡核苷酸（INH-ODNs）优先阻断体外自身抗原诱导的 B 细胞和树突状细胞活化以及狼疮易感 MRL-Fas(lpr/lpr)小鼠体内自身抗体的产生。
Arthritis Res Ther. 2009;11(3):R79. doi: 10.1186/ar2710. Epub 2009 May 28.
5
Toll-like receptor 7-dependent loss of B cell tolerance in pathogenic autoantibody knockin mice.致病性自身抗体敲入小鼠中Toll样受体7依赖性B细胞耐受性丧失
Immunity. 2006 Sep;25(3):429-40. doi: 10.1016/j.immuni.2006.07.014.
6
Toll-like receptor 7 cooperates with IL-4 in activated B cells through antigen receptor or CD38 and induces class switch recombination and IgG1 production.Toll样受体7在活化的B细胞中通过抗原受体或CD38与白细胞介素-4协同作用，诱导类别转换重排和IgG1产生。
Mol Immunol. 2009 Apr;46(7):1278-88. doi: 10.1016/j.molimm.2008.11.022. Epub 2009 Jan 20.
7
Activation of rheumatoid factor-specific B cells is antigen dependent and occurs preferentially outside of germinal centers in the lupus-prone NZM2410 mouse model.类风湿因子特异性 B 细胞的激活是抗原依赖性的，并且在狼疮易感 NZM2410 小鼠模型中优先发生在生发中心之外。
J Immunol. 2014 Aug 15;193(4):1609-21. doi: 10.4049/jimmunol.1303000. Epub 2014 Jul 11.
8
Critical role of TLR7 in the acceleration of systemic lupus erythematosus in TLR9-deficient mice.TLR7 在 TLR9 缺陷型小鼠全身性红斑狼疮加速发病中的关键作用。
J Autoimmun. 2010 Jun;34(4):339-48. doi: 10.1016/j.jaut.2009.11.001. Epub 2009 Nov 26.
9
Engagement of the B cell receptor for antigen differentially affects B cell responses to Toll-like receptor-7 agonists and antagonists in BXSB mice.抗原 B 细胞受体的结合对 BXSB 小鼠 Toll 样受体 7 激动剂和拮抗剂的 B 细胞反应有不同影响。
Clin Exp Immunol. 2011 Mar;163(3):392-403. doi: 10.1111/j.1365-2249.2010.04307.x. Epub 2011 Jan 14.
10
Emerging roles of TLR7 and TLR9 in murine SLE.TLR7 和 TLR9 在鼠类 SLE 中的新作用。
J Autoimmun. 2009 Nov-Dec;33(3-4):231-8. doi: 10.1016/j.jaut.2009.10.001. Epub 2009 Oct 21.

引用本文的文献

1
Involvement of nucleic acid-sensing toll-like receptors in human diseases and their controlling mechanisms.核酸传感Toll样受体在人类疾病中的作用及其调控机制。
J Biomed Sci. 2025 Jun 10;32(1):56. doi: 10.1186/s12929-025-01151-9.
2
What's atypical about human B cells after allogeneic stem cell transplantation?同种异体干细胞移植后人类B细胞有哪些不典型之处？
J Leukoc Biol. 2025 May 7;117(5). doi: 10.1093/jleuko/qiaf048.
3
Critical roles of chronic BCR signaling in the differentiation of anergic B cells into age-associated B cells in aging and autoimmunity.

本文引用的文献

1
Toll-like receptor 9 controls anti-DNA autoantibody production in murine lupus.Toll样受体9控制小鼠狼疮中抗DNA自身抗体的产生。
J Exp Med. 2005 Jul 18;202(2):321-31. doi: 10.1084/jem.20050338.
2
Plasmacytoid dendritic cells control TLR7 sensitivity of naive B cells via type I IFN.浆细胞样树突状细胞通过I型干扰素控制初始B细胞的TLR7敏感性。
J Immunol. 2005 Apr 1;174(7):4043-50. doi: 10.4049/jimmunol.174.7.4043.
3
Interleukin-18 receptor signaling is not required for autoantibody production and end-organ disease in murine lupus.
慢性B细胞受体信号在衰老和自身免疫过程中无反应性B细胞分化为年龄相关B细胞中的关键作用。
Sci Adv. 2025 Apr 18;11(16):eadt8199. doi: 10.1126/sciadv.adt8199.
4
Coordinated Regulation of Extrafollicular B Cell Responses by IL-12 and IFNγ.IL-12和IFNγ对滤泡外B细胞反应的协同调节
Immunol Rev. 2025 May;331(1):e70027. doi: 10.1111/imr.70027.
5
Cell surface RNA biology: new roles for RNA binding proteins.细胞表面RNA生物学：RNA结合蛋白的新作用
Trends Biochem Sci. 2025 May;50(5):402-416. doi: 10.1016/j.tibs.2025.03.005. Epub 2025 Mar 28.
6
B cell dysfunction in chronic hepatitis B virus infection.慢性乙型肝炎病毒感染中的B细胞功能障碍。
Liver Res. 2020 Sep 28;5(1):11-15. doi: 10.1016/j.livres.2020.09.004. eCollection 2021 Mar.
7
Opportunities and limitations of B cell depletion approaches in SLE.系统性红斑狼疮中B细胞清除疗法的机遇与局限
Nat Rev Rheumatol. 2025 Feb;21(2):111-126. doi: 10.1038/s41584-024-01210-9. Epub 2025 Jan 15.
8
A B cell screen against endogenous retroviruses identifies glycan-reactive IgM that recognizes a broad array of enveloped viruses.B 细胞针对内源性逆转录病毒的筛选鉴定出了糖基反应性 IgM，该 IgM 可识别广泛的包膜病毒。
Sci Immunol. 2024 Nov 8;9(101):eadd6608. doi: 10.1126/sciimmunol.add6608.
9
Polarization of the memory B-cell response.记忆B细胞反应的极化
J Leukoc Biol. 2025 Mar 14;117(3). doi: 10.1093/jleuko/qiae228.
10
Ro60-Roles in RNA Processing, Inflammation, and Rheumatic Autoimmune Diseases.Ro60-在 RNA 处理、炎症和风湿性自身免疫疾病中的作用。
Int J Mol Sci. 2024 Jul 14;25(14):7705. doi: 10.3390/ijms25147705.
白细胞介素-18受体信号传导在小鼠狼疮的自身抗体产生和终末器官疾病中并非必需。
Arthritis Rheum. 2005 Mar;52(3):984-6. doi: 10.1002/art.20961.
4
Human lupus autoantibody-DNA complexes activate DCs through cooperation of CD32 and TLR9.人类狼疮自身抗体 - DNA 复合物通过 CD32 和 TLR9 的协同作用激活树突状细胞。
J Clin Invest. 2005 Feb;115(2):407-17. doi: 10.1172/JCI23025.
5
The emerging role of interferon in human systemic lupus erythematosus.干扰素在人类系统性红斑狼疮中的新作用。
Curr Opin Immunol. 2004 Dec;16(6):801-7. doi: 10.1016/j.coi.2004.09.014.
6
Comparison of CpG s-ODNs, chromatin immune complexes, and dsDNA fragment immune complexes in the TLR9-dependent activation of rheumatoid factor B cells.类风湿因子B细胞TLR9依赖性激活中CpG硫代磷酸化寡脱氧核苷酸、染色质免疫复合物和双链DNA片段免疫复合物的比较
J Endotoxin Res. 2004;10(4):247-51. doi: 10.1179/096805104225005850.
7
Toll-like receptor 9-dependent and -independent dendritic cell activation by chromatin-immunoglobulin G complexes.染色质-免疫球蛋白G复合物通过Toll样受体9依赖性和非依赖性途径激活树突状细胞
J Exp Med. 2004 Jun 21;199(12):1631-40. doi: 10.1084/jem.20031942. Epub 2004 Jun 14.
8
TLR7: A new sensor of viral infection.Toll样受体7：病毒感染的新型感受器
Proc Natl Acad Sci U S A. 2004 May 4;101(18):6835-6. doi: 10.1073/pnas.0401347101. Epub 2004 Apr 27.
9
Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8.通过Toll样受体7和8对单链RNA进行物种特异性识别。
Science. 2004 Mar 5;303(5663):1526-9. doi: 10.1126/science.1093620. Epub 2004 Feb 19.
10
Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA.通过Toll样受体7介导的单链RNA识别产生的先天性抗病毒反应。
Science. 2004 Mar 5;303(5663):1529-31. doi: 10.1126/science.1093616. Epub 2004 Feb 19.