B cell-derived IL-27 promotes control of persistent LCMV infection

Isaraphorn Pratumchai, Jaroslav Zak, Zhe Huang, Booki Min, Michael B.A. Oldstone*, John R. Teijaro

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Recent studies have identified a critical role for B cell-produced cytokines in regulating both humoral and cellular immunity. Here, we show that B cells are an essential source of interleukin-27 (IL-27) during persistent lymphocytic choriomeningitis virus (LCMV) clone 13 (Cl-13) infection. By using conditional knockout mouse models with specific IL-27p28 deletion in B cells, we observed that B cell-derived IL-27 promotes survival of virus-specific CD4 T cells and supports functions of T follicular helper (Tfh) cells. Mechanistically, B cell-derived IL-27 promotes CD4 T cell function, antibody class switch, and the ability to control persistent LCMV infection. Deletion of IL-27ra in T cells demonstrated that T cell-intrinsic IL-27R signaling is essential for viral control, optimal CD4 T cell responses, and antibody class switch during persistent LCMV infection. Collectively, our findings identify a cellular mechanism whereby B cell-derived IL-27 drives antiviral immunity and antibody responses through IL-27 signaling on T cells to promote control of LCMV Cl-13 infection.

Original languageEnglish (US)
Article numbere2116741119
JournalProceedings of the National Academy of Sciences of the United States of America
Volume119
Issue number3
DOIs
StatePublished - Jan 18 2022

Keywords

  • Antibody
  • B cells
  • CD4 T cells
  • IL-27
  • Viral infection

ASJC Scopus subject areas

  • General

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