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Modulation of B-cell tolerance by murine gammaherpesvirus 68 infection: requirement for Orf73 viral gene expression and follicular helper T cells. Immunology 2013 Jun;139(2):197-204

Date

01/15/2013

Pubmed ID

23311955

Pubmed Central ID

PMC3647186

DOI

10.1111/imm.12069

Scopus ID

2-s2.0-84876816256   7 Citations

Abstract

Viruses such as Epstein-Barr virus (EBV) have been linked to mechanisms that support autoantibody production in diseases such as systemic lupus erythematosus. However, the mechanisms by which viruses contribute to autoantibody production remain poorly defined. This stems in part, from the high level of seropositivity for EBV (> 95%) and the exquisite species specificity of EBV. In this study we overcame these problems by using murine gammaherpesvirus 68 (MHV68), a virus genetically and biologically related to EBV. We first showed that MHV68 drives autoantibody production by promoting a loss of B-cell anergy. We next showed that MHV68 infection resulted in the expansion of follicular helper T (Tfh) cells in vivo, and that these Tfh cells supported autoantibody production and a loss of B-cell anergy. Finally, we showed that the expansion of Tfh cells and autoantibody production was dependent on the establishment of viral latency and expression of a functional viral gene called Orf73. Collectively, our studies highlighted an unexpected role for viral latency in the development of autoantibodies following MHV68 infection and suggest that virus-induced expansion of Tfh cells probably plays a key role in the loss of B-cell anergy.

Author List

Gauld SB, De Santis JL, Kulinski JM, McGraw JA, Leonardo SM, Ruder EA, Maier W, Tarakanova VL

Author

Vera Tarakanova PhD Associate Professor in the Microbiology and Immunology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Autoantibodies
B-Lymphocytes
Cell Proliferation
Cells, Cultured
Clonal Anergy
Coculture Techniques
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Host-Pathogen Interactions
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Microscopy, Fluorescence
Mutation
Rhadinovirus
T-Lymphocytes, Helper-Inducer
Viral Proteins
Virus Latency
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a