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

Proceedings of the National Academy of Sciences of the United States of America 2022 Jan 18

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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. Copyright © 2022 the Author(s). Published by PNAS.

Citation

Isaraphorn Pratumchai, Jaroslav Zak, Zhe Huang, Booki Min, Michael B A Oldstone, John R Teijaro. B cell-derived IL-27 promotes control of persistent LCMV infection. Proceedings of the National Academy of Sciences of the United States of America. 2022 Jan 18;119(3)