Blimp-1-dependent plasma cell differentiation is required for efficient maintenance of murine gammaherpesvirus latency and antiviral antibody responses

Andrea M. Siegel, Udaya Shankari Rangaswamy, Ruth J. Napier, Samuel H. Speck

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Recent evidence from the study of Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus supports a model in which terminal differentiation of B cells to plasma cells leads to virus reactivation. Here we address the role of Blimp-1, the master transcriptional regulator of plasma cell differentiation, in murine gammaherpesvirus 68 (MHV68) latency and reactivation. Blimp-1 expression in infected cells was dispensable for acute virus replication in the lung following intranasal inoculation and in the spleen following intraperitoneal inoculation with MHV68. However, we observed a role for Blimp-1 in both the establishment of latency and reactivation from latency in vivo. Additionally, plasma cell-deficient mice also exhibited a significant defect in the establishment of latency in the spleen, as well as reactivation from latency, similar to mice that lacked Blimp-1 only in MHV68-infected cells. In the absence of plasma cells, MHV68 infection failed to elicit a strong germinal center response and fewer B cells in the germinal center were MHV68 infected. Notably, the absence of a functional Blimp-1 gene only in MHV68-infected cells led to a decrease in both B-cell and CD4+ T-cell responses during the establishment of latency. Finally, Blimp-1 expression in infected cells played a critical role in the maintenance of both MHV68 latency in the spleen and antibody responses to MHV68. Together, these studies support a model wherein episodic Blimp-1-mediated plasma cell differentiation leads to MHV68 reactivation, which serves to both renew the latency reservoirs and stimulate long-lived plasma cells to secrete virus-specific antibody.

Original languageEnglish (US)
Pages (from-to)674-685
Number of pages12
JournalJournal of virology
Volume84
Issue number2
DOIs
StatePublished - Jan 2010
Externally publishedYes

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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