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Immunology ; 139(2): 197-204, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23311955

RESUMO

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.


Assuntos
Linfócitos B/imunologia , Rhadinovirus/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Proteínas Virais/imunologia , Animais , Autoanticorpos/imunologia , Linfócitos B/virologia , Proliferação de Células , Células Cultivadas , Anergia Clonal/imunologia , Técnicas de Cocultura , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Interações Hospedeiro-Patógeno/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Microscopia de Fluorescência , Mutação , Rhadinovirus/genética , Rhadinovirus/fisiologia , Linfócitos T Auxiliares-Indutores/virologia , Proteínas Virais/genética , Proteínas Virais/metabolismo , Latência Viral/genética , Latência Viral/imunologia
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