Induction of broadly reactive influenza antibodies increases susceptibility to autoimmunity
Jocelyn G. Labombarde,
Meenu R. Pillai,
Marie Wehenkel,
Chun-Yang Lin,
Rachael Keating,
Scott A. Brown,
Jeremy Chase Crawford,
David C. Brice,
Ashley H. Castellaw,
Alexandra H. Mandarano,
Clifford S. Guy,
Juan R. Mejia,
Carlessia D. Lewis,
Ti-Cheng Chang,
Christine M. Oshansky,
Sook-San Wong,
Richard J. Webby,
Mei Yan,
Quan–Zhen Li,
Tony N. Marion,
Paul G. Thomas,
Maureen A. McGargill
Affiliations
Jocelyn G. Labombarde
Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
Meenu R. Pillai
Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
Marie Wehenkel
Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
Chun-Yang Lin
Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA; Integrated Biomedical Sciences Program, University of Tennessee Health Science Center, Memphis, TN 38163, USA
Rachael Keating
Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
Scott A. Brown
Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
Jeremy Chase Crawford
Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
David C. Brice
Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
Ashley H. Castellaw
Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
Alexandra H. Mandarano
Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
Clifford S. Guy
Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
Juan R. Mejia
Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
Carlessia D. Lewis
Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
Ti-Cheng Chang
Center for Applied Bioinformatics, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
Christine M. Oshansky
Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
Sook-San Wong
Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
Richard J. Webby
Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
Mei Yan
Department of Immunology and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Quan–Zhen Li
Department of Immunology and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Tony N. Marion
Department of Microbiology, Immunology and Biochemistry, The University of Tennessee Health Science Center, Memphis, TN 38163, USA
Paul G. Thomas
Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
Maureen A. McGargill
Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA; Corresponding author
Summary: Infection and vaccination repeatedly expose individuals to antigens that are conserved between influenza virus subtypes. Nevertheless, antibodies recognizing variable influenza epitopes greatly outnumber antibodies reactive against conserved epitopes. Elucidating factors contributing to the paucity of broadly reactive influenza antibodies remains a major obstacle for developing a universal influenza vaccine. Here, we report that inducing broadly reactive influenza antibodies increases autoreactive antibodies in humans and mice and exacerbates disease in four distinct models of autoimmune disease. Importantly, transferring broadly reactive influenza antibodies augments disease in the presence of inflammation or autoimmune susceptibility. Further, broadly reactive influenza antibodies spontaneously arise in mice with defects in B cell tolerance. Together, these data suggest that self-tolerance mechanisms limit the prevalence of broadly reactive influenza antibodies, which can exacerbate disease in the context of additional risk factors.