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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.

Author information

1
Laboratory of Immune Regulation, Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan.
2
Laboratory of Infectious Diseases and Immunity.
3
Laboratory of Immunobiologics Evaluation, Center for Vaccine and Adjuvant Research, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka, Japan.
4
Department of Pharmaceutical Engineering, Graduate School of Engineering, Toyama Prefectural University.
5
Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
6
Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
7
Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.
8
Department of Immunology and Pathology, Monash University, Victoria, Australia.

Abstract

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.

KEYWORDS:

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

PMID:
31504561
DOI:
10.1093/intimm/dxz057

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