T-bet+ B cells are activated by and control endogenous retroviruses through TLR-dependent mechanisms

被引：10

作者：

Rauch, Eileen ^{[1
,12
]}

Amendt, Timm ^{[1
,13
]}

Krol, Aleksandra Lopez ^{[1
]}

Lang, Fabian B. ^{[1
]}

Linse, Vincent ^{[1
]}

Hohmann, Michelle ^{[1
,14
]}

Keim, Ann-Christin ^{[1
]}

Kreutzer, Susanne ^{[2
]}

Kawengian, Kevin ^{[1
]}

Buchholz, Malte ^{[3
,4
]}

Duschner, Philipp ^{[1
]}

Grauer, Saskia ^{[1
]}

Schnierle, Barbara ^{[5
]}

Ruhl, Andreas ^{[1
,15
]}

Burtscher, Ingo ^{[6
]}

Dehnert, Sonja ^{[1
]}

Kuria, Chege ^{[7
]}

Kupke, Alexandra ^{[8
]}

Paul, Stephanie ^{[1
]}

Liehr, Thomas ^{[9
]}

Lechner, Marcus ^{[10
]}

Schnare, Markus ^{[1
]}

Kaufmann, Andreas ^{[1
]}

Huber, Magdalena ^{[11
]}

Winkler, Thomas H. ^{[7
]}

Bauer, Stefan ^{[1
]}

Yu, Philipp ^{[1
]}

机构：

[1] Philipps Univ Marburg, Inst Pathol, D-35043 Marburg, Germany

[2] Max Planck Inst Heart & Lung Res, D-61231 Bad Nauheim, Germany

[3] Philipps Univ Marburg, Dept Gastroenterol Endocrinol & Metab, Marburg, Germany

[4] Philipps Univ Marburg, Core Facil Small Anim Multispectral & Ultrasound I, D-35043 Marburg, Germany

[5] Paul Ehrlich Inst, Dept Virol, D-63225 Langen, Germany

[6] Inst Diabet & Regenerat Res, Helmholtz Zentrum Munchen, D-85764 Neuherberg, Germany

[7] Friedrich Alexander Univ Erlangen Nurnberg, Nikolaus Fiebiger Ctr Mol Med, Gluckstr 6, D-91054 Erlangen, Germany

[8] Philipps Univ Marburg, Inst Virol, D-35043 Marburg, Germany

[9] Jena Univ Hosp, Friedrich Schiller Univ, Inst Human Genet, D-07747 Jena, Germany

[10] Philipps Univ Marburg, Ctr Synthet Microbiol, D-35043 Marburg, Germany

[11] Philipps Univ Marburg, Inst Sytems Immunol, Ctr Tumor & Immunobiol, D-35043 Marburg, Germany

[12] CSL Behring Innovat GmbH, Emil Von Behring Str 76, D-35041 Marburg, Germany

[13] Francis Crick Inst, London NW1 1AT, England

[14] Apollo Ventures Holding GmbH, D-20457 Hamburg, Germany

[15] Univ Hosp Erlangen, Dept Infect Biol, D-91054 Erlangen, Germany

来源：

NATURE COMMUNICATIONS | 2024年 / 15卷 / 01期

关键词：

MURINE LEUKEMIA-VIRUS; TOLL-LIKE RECEPTORS; IFN-GAMMA RECEPTOR; IMMUNE-RESPONSES; T-BET; MICE; ANTIBODY; RNA; IGE; GENERATION;

D O I：

10.1038/s41467-024-45201-6

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Endogenous retroviruses (ERVs) are an integral part of the mammalian genome. The role of immune control of ERVs in general is poorly defined as is their function as anti-cancer immune targets or drivers of autoimmune disease. Here, we generate mouse-strains where Moloney-Murine Leukemia Virus tagged with GFP (ERV-GFP) infected the mouse germline. This enables us to analyze the role of genetic, epigenetic and cell intrinsic restriction factors in ERV activation and control. We identify an autoreactive B cell response against the neo-self/ERV antigen GFP as a key mechanism of ERV control. Hallmarks of this response are spontaneous ERV-GFP+ germinal center formation, elevated serum IFN-gamma levels and a dependency on Age-associated B cells (ABCs) a subclass of T-bet+ memory B cells. Impairment of IgM B cell receptor-signal in nucleic-acid sensing TLR-deficient mice contributes to defective ERV control. Although ERVs are a part of the genome they break immune tolerance, induce immune surveillance against ERV-derived self-antigens and shape the host immune response.

引用

页数：19

共 82 条

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