Effects of Friend Virus Infection and Regulatory T Cells on the Antigen Presentation Function of B Cells

ABSTRACT Friend virus (FV) is a naturally occurring mouse retrovirus that infects dividing cells of the hematopoietic lineage, including antigen-presenting cells (APCs). The infection of APCs by viruses often induces their dysfunction, and it has been shown that FV infection reduces the ability of d...

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Autores principales:	Tyler C. Moore, Ronald J. Messer, Lorena M. Gonzaga, Jennifer M. Mather, Aaron B. Carmody, Wibke Bayer, Elisabeth Littwitz-Salomon, Ulf Dittmer, Kim J. Hasenkrug
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	B-cell responses CD8+ T cells antigen presentation regulatory T cells retroviruses Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/82fdd1ee430040aa8b8dfc433ed7d4b6
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spelling	oai:doaj.org-article:82fdd1ee430040aa8b8dfc433ed7d4b62021-11-15T15:55:13ZEffects of Friend Virus Infection and Regulatory T Cells on the Antigen Presentation Function of B Cells10.1128/mBio.02578-182150-7511https://doaj.org/article/82fdd1ee430040aa8b8dfc433ed7d4b62019-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02578-18https://doaj.org/toc/2150-7511ABSTRACT Friend virus (FV) is a naturally occurring mouse retrovirus that infects dividing cells of the hematopoietic lineage, including antigen-presenting cells (APCs). The infection of APCs by viruses often induces their dysfunction, and it has been shown that FV infection reduces the ability of dendritic cells (DCs) to prime critical CD8+ T cell responses. Nonetheless, mice mount vigorous CD8+ T cell responses, so we investigated whether B cells might serve as alternative APCs during FV infection. Direct ex vivo analysis of B cells from FV-infected mice revealed that infected but not uninfected B cells upregulated expression of the costimulatory molecules CD80, CD86, and CD40, as well as major histocompatibility complex class II (MHC-II) molecules. Furthermore, in vitro studies showed that, compared to uninfected B cells from the same mice, the FV-infected B cells had significantly enhanced APC function, as measured by their capacity to prime CD8+ T cell activation and proliferation. Thus, in contrast to DCs, infection of B cells with FV enhanced their APC capacity and ability to stimulate the CD8+ T cell responses essential for virus control. FV infections also induce the activation and expansion of regulatory T cells (Tregs), so it was of interest to determine the impact of Tregs on B cell activation. The upregulation of costimulatory molecule expression and APC function of B cells was even more strongly enhanced by in vivo depletion of regulatory T cells than infection. Thus, Tregs exert potent homeostatic suppression of B cell activation that is partially overcome by FV infection. IMPORTANCE The primary role of B cells in immunity is considered the production of pathogen-specific antibodies, but another, less-well-studied, function of B cells is to present foreign antigens to T cells to stimulate their activation and proliferation. Dendritic cells (DCs) are considered the most important antigen-presenting cells (APCs) for CD8+ T cells, but DCs lose APC function when infected with Friend virus (FV), a model retrovirus of mice. Interestingly, B cells were better able to stimulate CD8+ T cell responses when they were infected with FV. We also found that the activation status of B cells under homeostatic conditions was potently modulated by regulatory T cells. This study illustrates an important link between B cell and T cell responses and illustrates an additional mechanism by which regulatory T cells suppress critical T cell responses during viral infections.Tyler C. MooreRonald J. MesserLorena M. GonzagaJennifer M. MatherAaron B. CarmodyWibke BayerElisabeth Littwitz-SalomonUlf DittmerKim J. HasenkrugAmerican Society for MicrobiologyarticleB-cell responsesCD8+ T cellsantigen presentationregulatory T cellsretrovirusesMicrobiologyQR1-502ENmBio, Vol 10, Iss 1 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	B-cell responses CD8+ T cells antigen presentation regulatory T cells retroviruses Microbiology QR1-502
spellingShingle	B-cell responses CD8+ T cells antigen presentation regulatory T cells retroviruses Microbiology QR1-502 Tyler C. Moore Ronald J. Messer Lorena M. Gonzaga Jennifer M. Mather Aaron B. Carmody Wibke Bayer Elisabeth Littwitz-Salomon Ulf Dittmer Kim J. Hasenkrug Effects of Friend Virus Infection and Regulatory T Cells on the Antigen Presentation Function of B Cells
description	ABSTRACT Friend virus (FV) is a naturally occurring mouse retrovirus that infects dividing cells of the hematopoietic lineage, including antigen-presenting cells (APCs). The infection of APCs by viruses often induces their dysfunction, and it has been shown that FV infection reduces the ability of dendritic cells (DCs) to prime critical CD8+ T cell responses. Nonetheless, mice mount vigorous CD8+ T cell responses, so we investigated whether B cells might serve as alternative APCs during FV infection. Direct ex vivo analysis of B cells from FV-infected mice revealed that infected but not uninfected B cells upregulated expression of the costimulatory molecules CD80, CD86, and CD40, as well as major histocompatibility complex class II (MHC-II) molecules. Furthermore, in vitro studies showed that, compared to uninfected B cells from the same mice, the FV-infected B cells had significantly enhanced APC function, as measured by their capacity to prime CD8+ T cell activation and proliferation. Thus, in contrast to DCs, infection of B cells with FV enhanced their APC capacity and ability to stimulate the CD8+ T cell responses essential for virus control. FV infections also induce the activation and expansion of regulatory T cells (Tregs), so it was of interest to determine the impact of Tregs on B cell activation. The upregulation of costimulatory molecule expression and APC function of B cells was even more strongly enhanced by in vivo depletion of regulatory T cells than infection. Thus, Tregs exert potent homeostatic suppression of B cell activation that is partially overcome by FV infection. IMPORTANCE The primary role of B cells in immunity is considered the production of pathogen-specific antibodies, but another, less-well-studied, function of B cells is to present foreign antigens to T cells to stimulate their activation and proliferation. Dendritic cells (DCs) are considered the most important antigen-presenting cells (APCs) for CD8+ T cells, but DCs lose APC function when infected with Friend virus (FV), a model retrovirus of mice. Interestingly, B cells were better able to stimulate CD8+ T cell responses when they were infected with FV. We also found that the activation status of B cells under homeostatic conditions was potently modulated by regulatory T cells. This study illustrates an important link between B cell and T cell responses and illustrates an additional mechanism by which regulatory T cells suppress critical T cell responses during viral infections.
format	article
author	Tyler C. Moore Ronald J. Messer Lorena M. Gonzaga Jennifer M. Mather Aaron B. Carmody Wibke Bayer Elisabeth Littwitz-Salomon Ulf Dittmer Kim J. Hasenkrug
author_facet	Tyler C. Moore Ronald J. Messer Lorena M. Gonzaga Jennifer M. Mather Aaron B. Carmody Wibke Bayer Elisabeth Littwitz-Salomon Ulf Dittmer Kim J. Hasenkrug
author_sort	Tyler C. Moore
title	Effects of Friend Virus Infection and Regulatory T Cells on the Antigen Presentation Function of B Cells
title_short	Effects of Friend Virus Infection and Regulatory T Cells on the Antigen Presentation Function of B Cells
title_full	Effects of Friend Virus Infection and Regulatory T Cells on the Antigen Presentation Function of B Cells
title_fullStr	Effects of Friend Virus Infection and Regulatory T Cells on the Antigen Presentation Function of B Cells
title_full_unstemmed	Effects of Friend Virus Infection and Regulatory T Cells on the Antigen Presentation Function of B Cells
title_sort	effects of friend virus infection and regulatory t cells on the antigen presentation function of b cells
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/82fdd1ee430040aa8b8dfc433ed7d4b6
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Effects of Friend Virus Infection and Regulatory T Cells on the Antigen Presentation Function of B Cells

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