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Int Immunol. 2019 Aug 27. pii: dxz057. doi: 10.1093/intimm/dxz057. [Epub ahead of print]

Self-reactive and polyreactive B cells are generated and selected in the germinal center during γ-herpesvirus infection.

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Laboratory of Immune Regulation, Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan.
Laboratory of Infectious Diseases and Immunity.
Laboratory of Immunobiologics Evaluation, Center for Vaccine and Adjuvant Research, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka, Japan.
Department of Pharmaceutical Engineering, Graduate School of Engineering, Toyama Prefectural University.
Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.
Department of Immunology and Pathology, Monash University, Victoria, Australia.


Immune responses against certain viruses are accompanied by autoantibody production although the origin of these infection-associated autoantibodies is unclear. Here we report that murine γ-herpesvirus 68 (MHV68)-induced autoantibodies are derived from polyreactive B cells in germinal center (GC) through the activity of short-lived plasmablasts. The analysis of recombinant antibodies from MHV68-infected mice revealed that about 40% of IgG+ GC B cells were self-reactive, with about half of them being polyreactive. On the other hand, virion-reactive clones accounted for only a minor proportion of IgG+ GC B cells, half of which also reacted with self-antigens. The self-reactivity of most polyreactive clones was dependent on somatic hypermutation (SHM), but this was dispensable for the reactivity of virus mono-specific clones. Furthermore, both virus-mono-specific and polyreactive clones were selected to differentiate to B220lo CD138+ plasma cells (PCs). However, the representation of GC-derived polyreactive clones was reduced and that of virus-mono-specific clones was markedly increased in terminally differentiated PCs as compared to transient plasmablasts. Collectively, our findings demonstrate that, during acute MHV68 infection, self-reactive B cells are generated through SHM and selected for further differentiation to short-lived plasmablasts but not terminally differentiated PCs.


autoimmunity; polyreactive antibody; post-GC tolerance; viral infection


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