PMID- 30670616 OWN - NLM STAT- MEDLINE DCOM- 20190405 LR - 20200309 IS - 2150-7511 (Electronic) VI - 10 IP - 1 DP - 2019 Jan 22 TI - Effects of Friend Virus Infection and Regulatory T Cells on the Antigen Presentation Function of B Cells. LID - 10.1128/mBio.02578-18 [doi] LID - e02578-18 AB - 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. FAU - Moore, Tyler C AU - Moore TC AD - Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA. FAU - Messer, Ronald J AU - Messer RJ AD - Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA. FAU - Gonzaga, Lorena M AU - Gonzaga LM AD - Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA. FAU - Mather, Jennifer M AU - Mather JM AD - Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA. FAU - Carmody, Aaron B AU - Carmody AB AD - Research Technologies Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA. FAU - Bayer, Wibke AU - Bayer W AUID- ORCID: 0000-0002-5885-5592 AD - Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany. FAU - Littwitz-Salomon, Elisabeth AU - Littwitz-Salomon E AD - Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany. FAU - Dittmer, Ulf AU - Dittmer U AD - Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany. FAU - Hasenkrug, Kim J AU - Hasenkrug KJ AUID- ORCID: 0000-0001-8523-4911 AD - Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA khasenkrug@nih.gov. LA - eng PT - Journal Article PT - Research Support, N.I.H., Intramural PT - Research Support, Non-U.S. Gov't DEP - 20190122 PL - United States TA - mBio JT - mBio JID - 101519231 RN - 0 (B7-1 Antigen) RN - 0 (B7-2 Antigen) RN - 0 (CD40 Antigens) RN - 0 (Histocompatibility Antigens Class II) SB - IM MH - Animals MH - *Antigen Presentation MH - B-Lymphocytes/chemistry/*immunology MH - B7-1 Antigen/analysis MH - B7-2 Antigen/analysis MH - CD40 Antigens/analysis MH - CD8-Positive T-Lymphocytes/immunology MH - Cell Proliferation MH - Friend murine leukemia virus/*immunology MH - Histocompatibility Antigens Class II/analysis MH - Leukemia, Experimental/immunology/virology MH - Lymphocyte Activation MH - Mice MH - Retroviridae Infections/immunology/virology MH - T-Lymphocytes, Regulatory/*immunology MH - Tumor Virus Infections/immunology/virology PMC - PMC6343038 OTO - NOTNLM OT - B-cell responses OT - CD8+ T cells OT - antigen presentation OT - regulatory T cells OT - retroviruses EDAT- 2019/01/24 06:00 MHDA- 2019/04/06 06:00 PMCR- 2019/01/22 CRDT- 2019/01/24 06:00 PHST- 2019/01/24 06:00 [entrez] PHST- 2019/01/24 06:00 [pubmed] PHST- 2019/04/06 06:00 [medline] PHST- 2019/01/22 00:00 [pmc-release] AID - mBio.02578-18 [pii] AID - mBio02578-18 [pii] AID - 10.1128/mBio.02578-18 [doi] PST - epublish SO - mBio. 2019 Jan 22;10(1):e02578-18. doi: 10.1128/mBio.02578-18.