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

Shuhei Sakakibara, Teruhito Yasui, Hideyuki Jinzai, Kristy O’Donnell, Chao Yuan Tsai, Takeharu Minamitani, Kazuya Takeda, Gabrielle T. Belz, David M. Tarlinton, Hitoshi Kikutani

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7 Citations (Scopus)


Immune responses against certain viruses are accompanied by auto-antibody production although the origin of these infection-associated auto-antibodies is unclear. Here, we report that murine γ-herpesvirus 68 (MHV68)-induced auto-antibodies are derived from polyreactive B cells in the 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.

Original languageEnglish
Pages (from-to)27-38
Number of pages12
JournalInternational Immunology
Issue number1
Publication statusPublished - Jan 2020


  • Autoimmunity
  • Polyreactive antibody
  • Post-GC tolerance
  • Viral infection

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