Using IL-27p28 reporter mice, Pratumchai et al. showed that IL-27-producing B/plasma cells are essential for control of persistent LCMV infection. Mice lacking IL-27 receptor (IL-27ra) expression in B cells or granzyme B+ cells controlled virus, but mice with T cell-specific conditional IL-27ra KO did not. Mice lacking B cell-specific IL-27p28 expression or mice with CD4+ T cell-specific IL-27ra KO did not control serum and tissue LCMV loads, and had fewer virus-specific CD8+ T cells (but no defect in cytokine production), virus-specific IFNγ-producing CD4+ T and IFNγ+IL-21+ Tfh cells (cytokines critical for CD8+ T cell development), and reduced antibody class switching.
Contributed by Paula Hochman
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.
Author Info: (1) Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037. Department of Immunology, Leiden University Medical Center, Leiden 2333 ZA, The N
Author Info: (1) Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037. Department of Immunology, Leiden University Medical Center, Leiden 2333 ZA, The Netherlands. (2) Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037. (3) Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037. (4) Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611. (5) Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037; mbaobo@scripps.edu teijaro@scripps.edu. (6) Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037; mbaobo@scripps.edu teijaro@scripps.edu.
