title: Essential role for autophagy in the maintenance of immunological memory against influenza infection.
abstract: Vaccination has been the most widely used strategy to protect against viral infections for centuries. However, the molecular mechanisms governing the long-term persistence of immunological memory in response to vaccines remain unclear. Here we show that autophagy has a critical role in the maintenance of memory B cells that protect against influenza virus infection. Memory B cells displayed elevated levels of basal autophagy with increased expression of genes that regulate autophagy initiation or autophagosome maturation. Mice with B cell-specific deletion of Atg7 (B/Atg7(-/-) mice) showed normal primary antibody responses after immunization against influenza but failed to generate protective secondary antibody responses when challenged with influenza viruses, resulting in high viral loads, widespread lung destruction and increased fatality. Our results suggest that autophagy is essential for the survival of virus-specific memory B cells in mice and the maintenance of protective antibody responses required to combat infections.
authors.affiliation: Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Monica Jeongsoo
authors.initials: MJ
authors.lastname: Hong
authors.affiliation: Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Huanhuan
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Xiurong
authors.initials: X
authors.lastname: Shi
authors.affiliation: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Brian E
authors.initials: BE
authors.lastname: Gilbert
authors.affiliation: 1] Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA. [2] Department of Medicine, Baylor College of Medicine, Houston, Texas, USA. [3] Biology of Inflammation Center, Baylor College of Medicine, Houston, Texas, USA. [4] Center for Translational Research on Inflammatory Diseases, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA.
authors.forename: David B
authors.initials: DB
authors.lastname: Corry
authors.affiliation: 1] Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA. [2] Department of Medicine, Baylor College of Medicine, Houston, Texas, USA. [3] Biology of Inflammation Center, Baylor College of Medicine, Houston, Texas, USA. [4] Center for Translational Research on Inflammatory Diseases, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA.
authors.forename: Farrah
authors.initials: F
authors.lastname: Kheradmand
authors.affiliation: Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000276:immunology; D001343:Autophagy / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D006801:Humans; D007114:Immunization; D007156:Immunologic Memory; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D007252:Influenza Vaccines / Q000627:therapeutic use; D007251:Influenza, Human / Q000276:immunology*; D051379:Mice
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines
references.citation: Immunol Rev. 2010 Sep;237(1):104-16
references.pmid: 20727032
references.citation: J Immunol. 1997 Oct 15;159(8):3816-22
references.pmid: 9378969
references.citation: Nature. 2011 Feb 24;470(7335):543-7
references.pmid: 21350488
references.citation: Chest. 2013 Feb 1;143(2):502-510
references.pmid: 23381315
references.citation: Curr Opin Immunol. 2006 Jun;18(3):255-64
references.pmid: 16632337
references.citation: Autophagy. 2008 Apr;4(3):309-14
references.pmid: 18188005
references.citation: J Immunol. 2002 Nov 15;169(10):5904-11
references.pmid: 12421974
references.citation: J Immunol. 1998 May 15;160(10):4688-95
references.pmid: 9590214
references.citation: J Cell Sci. 2004 Jun 1;117(Pt 13):2805-12
references.pmid: 15169837
references.citation: Vaccine. 2012 Aug 31;30(40):5893-900
references.pmid: 22835738
references.citation: Nat Immunol. 2011 Jul 10;12(8):786-95
references.pmid: 21743478
references.citation: Immunity. 2009 Feb 20;30(2):180-92
references.pmid: 19239902
references.citation: Annu Rev Immunol. 2005;23:487-513
references.pmid: 15771579
references.citation: PLoS Med. 2004 Oct;1(1):e8
references.pmid: 15526056
references.citation: Mol Cell Biol. 2000 Aug;20(15):5680-9
references.pmid: 10891504
references.citation: J Cell Biol. 2005 May 9;169(3):425-34
references.pmid: 15866887
references.citation: Cell Death Differ. 1997 Jul;4(5):396-402
references.pmid: 16465258
references.citation: Nature. 2009 Jun 18;459(7249):931-9
references.pmid: 19525932
references.citation: Nat Rev Immunol. 2002 Dec;2(12):982-7
references.pmid: 12461571
references.citation: J Exp Med. 2000 Feb 7;191(3):475-84
references.pmid: 10662793
references.citation: Curr Opin Cell Biol. 2010 Apr;22(2):252-62
references.pmid: 20116986
references.citation: Nature. 2009 Jul 2;460(7251):108-12
references.pmid: 19543266
references.citation: Hum Vaccin. 2010 Jul;6(7):585-94
references.pmid: 20421727
references.citation: Free Radic Biol Med. 2002 Aug 15;33(4):473-90
references.pmid: 12160930
references.citation: Nat Rev Immunol. 2002 Sep;2(9):706-13
references.pmid: 12209139
references.citation: Arch Pharm Res. 2010 Nov;33(11):1813-23
references.pmid: 21116785
references.citation: Apoptosis. 2003 Aug;8(4):345-52
references.pmid: 12815277
references.citation: Dev Cell. 2004 Apr;6(4):463-77
references.pmid: 15068787
references.citation: Nature. 2000 Oct 5;407(6804):636-42
references.pmid: 11034213
references.citation: Immunol Rev. 2012 May;247(1):52-63
references.pmid: 22500831
references.citation: J Exp Med. 1997 Feb 3;185(3):563-71
references.pmid: 9053456
references.citation: Nature. 2006 Jun 15;441(7095):880-4
references.pmid: 16625205
references.citation: Biochimie. 2012 Jan;94(1):101-9
references.pmid: 21983178
references.citation: Science. 2011 Mar 4;331(6021):1203-7
references.pmid: 21310965
references.citation: Free Radic Res. 2010 Oct;44(10):1098-124
references.pmid: 20836659
references.citation: Nature. 2006 Jun 15;441(7095):885-9
references.pmid: 16625204
references.citation: Blood. 2007 Dec 1;110(12):3978-84
references.pmid: 17720882
references.citation: Nat Cell Biol. 2006 Jul;8(7):688-99
references.pmid: 16799551
references.citation: Nat Immunol. 2013 Mar;14(3):298-305
references.pmid: 23354484
references.citation: Nat Rev Immunol. 2011 Dec 09;12(1):24-34
references.pmid: 22158414
references.citation: J Cell Biol. 2008 May 5;181(3):497-510
references.pmid: 18443221
references.citation: Prostaglandins Other Lipid Mediat. 2009 Jan;88(1-2):51-61
references.pmid: 18984060
references.citation: J Cell Physiol. 1996 Nov;169(2):333-40
references.pmid: 8908200
references.citation: Proc Natl Acad Sci U S A. 1982 Mar;79(6):1889-92
references.pmid: 6952238
references.citation: Science. 2011 Aug 26;333(6046):1109-12
references.pmid: 21868666
references.citation: J Exp Ther Oncol. 2007;6(4):267-77
references.pmid: 18038760
references.citation: J Immunol. 2009 Jun 15;182(12):7353-63
references.pmid: 19494257
references.citation: Nat Immunol. 2011 Jun;12(6):509-17
references.pmid: 21739679
references.citation: Mucosal Immunol. 2011 Mar;4(2):197-207
references.pmid: 20736998
references.citation: Mol Biol Cell. 2008 Dec;19(12):5360-72
references.pmid: 18843052
references.citation: Proc Natl Acad Sci U S A. 1990 Jun;87(12):4781-4
references.pmid: 2352948
references.citation: Exp Eye Res. 1993 May;56(5):543-54
references.pmid: 8388805
references.citation: Nature. 2011 Jan 20;469(7330):323-35
references.pmid: 21248839
references.citation: Nat Rev Immunol. 2007 Jul;7(7):532-42
references.pmid: 17589543
references.citation: Nat Cell Biol. 2007 Oct;9(10):1102-9
references.pmid: 17909521
references.citation: Nat Rev Drug Discov. 2007 Apr;6(4):304-12
references.pmid: 17396135
references.citation: Nat Chem Biol. 2005 Jul;1(2):112-9
references.pmid: 16408008
references.citation: Nat Cell Biol. 2013 Jul;15(7):741-50
references.pmid: 23685627
references.citation: Blood. 2011 Oct 13;118(15):4120-8
references.pmid: 21868573
references.citation: Nature. 1999 Dec 9;402(6762):672-6
references.pmid: 10604474
references.citation: Nature. 2008 Sep 25;455(7212):532-6
references.pmid: 18716625
references.citation: Cell. 2005 Jan 28;120(2):237-48
references.pmid: 15680329
references.citation: Annu Rev Immunol. 1999;17:221-53
references.pmid: 10358758
references.citation: Immunity. 2001 Feb;14(2):181-92
references.pmid: 11239450