TY - JOUR
T1 - B cell-derived IL-27 promotes control of persistent LCMV infection
AU - Pratumchai, Isaraphorn
AU - Zak, Jaroslav
AU - Huang, Zhe
AU - Min, Booki
AU - Oldstone, Michael B.A.
AU - Teijaro, John R.
N1 - Publisher Copyright:
© This article is distributed under Creative Commons Attribution-NonCommercialNoDerivatives License 4.0 (CC BY-NC-ND).
PY - 2022/1/18
Y1 - 2022/1/18
N2 - 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.
AB - 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.
KW - Antibody
KW - B cells
KW - CD4 T cells
KW - IL-27
KW - Viral infection
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U2 - 10.1073/pnas.2116741119
DO - 10.1073/pnas.2116741119
M3 - Article
C2 - 35022243
AN - SCOPUS:85123093232
SN - 0027-8424
VL - 119
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 3
M1 - e2116741119
ER -