title: RETRACTED: MAVS, cGAS, and endogenous retroviruses in T-independent B cell responses.
abstract: Multivalent molecules with repetitive structures including bacterial capsular polysaccharides and viral capsids elicit antibody responses through B cell receptor (BCR) crosslinking in the absence of T cell help. We report that immunization with these T cell-independent type 2 (TI-2) antigens causes up-regulation of endogenous retrovirus (ERV) RNAs in antigen-specific mouse B cells. These RNAs are detected via a mitochondrial antiviral signaling protein (MAVS)-dependent RNA sensing pathway or reverse-transcribed and detected via the cGAS-cGAMP-STING pathway, triggering a second, sustained wave of signaling that promotes specific immunoglobulin M production. Deficiency of both MAVS and cGAS, or treatment of MAVS-deficient mice with reverse transcriptase inhibitors, dramatically inhibits TI-2 antibody responses. These findings suggest that ERV and two innate sensing pathways that detect them are integral components of the TI-2 B cell signaling apparatus.
authors.affiliation: Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8502, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Zeng
authors.affiliation: Department of Pediatrics and Children's Medical Center Research Institute, and McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8502, USA.
authors.forename: Zeping
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Pediatrics and Children's Medical Center Research Institute, and McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8502, USA.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Shi
authors.affiliation: Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8502, USA.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Li
authors.affiliation: Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8502, USA.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Zhan
authors.affiliation: Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8502, USA. Howard Hughes Medical Institute, Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9148, USA.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Li
authors.affiliation: Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8502, USA. Howard Hughes Medical Institute, Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9148, USA.
authors.forename: Jianhui
authors.initials: J
authors.lastname: Wang
authors.affiliation: Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8502, USA.
authors.forename: Jin Huk
authors.initials: JH
authors.lastname: Choi
authors.affiliation: Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8502, USA.
authors.forename: Kuan-wen
authors.initials: KW
authors.lastname: Wang
authors.affiliation: Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8502, USA.
authors.forename: Tiana
authors.initials: T
authors.lastname: Purrington
authors.affiliation: Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8502, USA.
authors.forename: Miao
authors.initials: M
authors.lastname: Tang
authors.affiliation: Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8502, USA.
authors.forename: Maggy
authors.initials: M
authors.lastname: Fina
authors.affiliation: Department of Pediatrics and Children's Medical Center Research Institute, and McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8502, USA.
authors.forename: Ralph J
authors.initials: RJ
authors.lastname: DeBerardinis
authors.affiliation: Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8502, USA.
authors.forename: Eva Marie Y
authors.initials: EM
authors.lastname: Moresco
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Nobels väg 16, SE-171 77 Stockholm, Sweden.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Pedersen
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Nobels väg 16, SE-171 77 Stockholm, Sweden.
authors.forename: Gerald M
authors.initials: GM
authors.lastname: McInerney
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Nobels väg 16, SE-171 77 Stockholm, Sweden.
authors.forename: Gunilla B
authors.initials: GB
authors.lastname: Karlsson Hedestam
authors.affiliation: Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8502, USA. Howard Hughes Medical Institute, Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9148, USA.
authors.forename: Zhijian J
authors.initials: ZJ
authors.lastname: Chen
authors.affiliation: Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8502, USA. Bruce.Beutler@UTSouthwestern.edu.
authors.forename: Bruce
authors.initials: B
authors.lastname: Beutler
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000917:Antibody Formation; D000955:Antigens, T-Independent / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D003600:Cytosol / Q000276:immunology; D004247:DNA / Q000276:immunology; D020077:Endogenous Retroviruses / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D009712:Nucleotides, Cyclic / Q000276:immunology; D009713:Nucleotidyltransferases / Q000235:genetics / Q000276:immunology*; D012367:RNA, Viral / Q000235:genetics / Q000276:immunology*; D014158:Transcription, Genetic; D000099197:STING Protein; D000099235:Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000955:Antigens, T-Independent; D004247:DNA; D008565:Membrane Proteins; D016328:NF-kappa B; D009712:Nucleotides, Cyclic; D009713:Nucleotidyltransferases; D012367:RNA, Viral; C512612:MAVS protein, mouse; C530855:Sting1 protein, mouse; D000099197:STING Protein; C584311:cyclic guanosine monophosphate-adenosine monophosphate; C578391:cGAS protein, mouse; D000099235:Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase