Cutting edge: B cell-intrinsic T-bet expression is required to control chronic viral infection

Burton E. Barnett; Ryan P. Staupe; Pamela M. Odorizzi; Olesya Palko; Vesselin T. Tomov; Alison E. Mahan; Bronwyn Gunn; Diana Chen; Michael A. Paley; Galit Alter; Steven L. Reiner; Georg M. Lauer; John R. Teijaro; E. John Wherry

doi:10.4049/jimmunol.1500368

Cutting edge: B cell-intrinsic T-bet expression is required to control chronic viral infection

Burton E. Barnett, Ryan P. Staupe, Pamela M. Odorizzi, Olesya Palko, Vesselin T. Tomov, Alison E. Mahan, Bronwyn Gunn, Diana Chen, Michael A. Paley, Galit Alter, Steven L. Reiner, Georg M. Lauer, John R. Teijaro, E. John Wherry

Research output: Contribution to journal › Article › peer-review

116 Scopus citations

Abstract

The role of Ab and B cells in preventing infection is established. In contrast, the role of B cell responses in containing chronic infections remains poorly understood. IgG2a (IgG1 in humans) can prevent acute infections, and T-bet promotes IgG2a isotype switching. However, whether IgG2a and B cell-expressed T-bet influence the host-pathogen balance during persisting infections is unclear. We demonstrate that B cell-specific loss of T-bet prevents control of persisting viral infection. T-bet in B cells controlled IgG2a production, as well as mucosal localization, proliferation, glycosylation, and a broad transcriptional program. T-bet controlled a broad antiviral program in addition to IgG2a because T-bet in B cells was important, even in the presence of virusspecific IgG2a. Our data support a model in which T-bet is a universal controller of antiviral immunity across multiple immune lineages.

Original language	English
Pages (from-to)	1017-1022
Number of pages	6
Journal	Journal of Immunology
Volume	197
Issue number	4
DOIs	https://doi.org/10.4049/jimmunol.1500368
State	Published - Aug 15 2016

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Barnett, B. E., Staupe, R. P., Odorizzi, P. M., Palko, O., Tomov, V. T., Mahan, A. E., Gunn, B., Chen, D., Paley, M. A., Alter, G., Reiner, S. L., Lauer, G. M., Teijaro, J. R., & Wherry, E. J. (2016). Cutting edge: B cell-intrinsic T-bet expression is required to control chronic viral infection. Journal of Immunology, 197(4), 1017-1022. https://doi.org/10.4049/jimmunol.1500368

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title = "Cutting edge: B cell-intrinsic T-bet expression is required to control chronic viral infection",

abstract = "The role of Ab and B cells in preventing infection is established. In contrast, the role of B cell responses in containing chronic infections remains poorly understood. IgG2a (IgG1 in humans) can prevent acute infections, and T-bet promotes IgG2a isotype switching. However, whether IgG2a and B cell-expressed T-bet influence the host-pathogen balance during persisting infections is unclear. We demonstrate that B cell-specific loss of T-bet prevents control of persisting viral infection. T-bet in B cells controlled IgG2a production, as well as mucosal localization, proliferation, glycosylation, and a broad transcriptional program. T-bet controlled a broad antiviral program in addition to IgG2a because T-bet in B cells was important, even in the presence of virusspecific IgG2a. Our data support a model in which T-bet is a universal controller of antiviral immunity across multiple immune lineages.",

author = "Barnett, {Burton E.} and Staupe, {Ryan P.} and Odorizzi, {Pamela M.} and Olesya Palko and Tomov, {Vesselin T.} and Mahan, {Alison E.} and Bronwyn Gunn and Diana Chen and Paley, {Michael A.} and Galit Alter and Reiner, {Steven L.} and Lauer, {Georg M.} and Teijaro, {John R.} and Wherry, {E. John}",

note = "Publisher Copyright: Copyright {\textcopyright} 2016 by The American Association of Immunologists, Inc.",

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doi = "10.4049/jimmunol.1500368",

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AU - Barnett, Burton E.

AU - Staupe, Ryan P.

AU - Odorizzi, Pamela M.

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AU - Tomov, Vesselin T.

AU - Mahan, Alison E.

AU - Gunn, Bronwyn

AU - Chen, Diana

AU - Paley, Michael A.

AU - Alter, Galit

AU - Reiner, Steven L.

AU - Lauer, Georg M.

AU - Teijaro, John R.

AU - Wherry, E. John

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AB - The role of Ab and B cells in preventing infection is established. In contrast, the role of B cell responses in containing chronic infections remains poorly understood. IgG2a (IgG1 in humans) can prevent acute infections, and T-bet promotes IgG2a isotype switching. However, whether IgG2a and B cell-expressed T-bet influence the host-pathogen balance during persisting infections is unclear. We demonstrate that B cell-specific loss of T-bet prevents control of persisting viral infection. T-bet in B cells controlled IgG2a production, as well as mucosal localization, proliferation, glycosylation, and a broad transcriptional program. T-bet controlled a broad antiviral program in addition to IgG2a because T-bet in B cells was important, even in the presence of virusspecific IgG2a. Our data support a model in which T-bet is a universal controller of antiviral immunity across multiple immune lineages.

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Cutting edge: B cell-intrinsic T-bet expression is required to control chronic viral infection

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