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.
