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

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 119; no. 3
• Main Authors: Pratumchai, Isaraphorn, Zak, Jaroslav, Huang, Zhe, Min, Booki, Oldstone, Michael B A, Teijaro, John R
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 18.01.2022
• Subjects: Adaptive Immunity; Animal models; Animals; Antibodies; Antibodies, Viral; B-Lymphocytes - metabolism; Biological Sciences; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; Cell-mediated immunity; Class switching; Clonal deletion; Cytokines; Cytokines - metabolism; Deletion; Humoral immunity; Immunity; Immunity, Cellular; Infections; Interleukin 27; Interleukin-27 - genetics; Interleukin-27 - metabolism; Interleukins; Lymphocytes; Lymphocytes B; Lymphocytes T; Lymphocytic Choriomeningitis - immunology; Lymphocytic choriomeningitis virus - immunology; Mice; Mice, Inbred C57BL; Mice, Knockout; Persistent infection; Signaling; Viruses; IL-27; CD4 T cells; antibody; viral infection; B cells
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2116741119

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.