Analysis of the virus-specific and nonspecific B cell response to a persistent B-lymphotropic gammaherpesvirus

Mark Y. Sangster, David J. Topham, Sybil D'Costa, Rhonda D. Cardin, Tony Marion, Linda Myers, Peter C. Doherty

Research output: Contribution to journalArticle

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Abstract

Respiratory challenge of mice with murine gammaherpesvirus 68 (γHV68) results in acute replication in respiratory epithelial cells and persistent, latent infection of B cells and macrophages. γHV68 elicits virus-specific Ab, and also nonspecifically activates B cells to Ab production through a CD4+ T cell-dependent process. The current analysis characterizes virus- specific and nonspecific Ab production at the single cell level and investigates the requirements and nature of the nonspecific response. Virus. specific Ab-forming cell (AFC) numbers were dwarfed by the increase in total AFC in all sites examined, indicating substantial nonspecific Ab production. Clear increases and decreases in specific and total AFC numbers occurred in the lymph nodes draining the respiratory tract and the spleen, but AFC numbers in the bone marrow (BM) increased to a plateau and remained constant. The longevity of the BM response was reflected in a sustained increase in virus-specific and total serum Ab levels. Generally, the IgG2a and IgG2b isotypes predominated. Analysis of cytokine-deficient mice, CD40 ligand- deficient mice, and radiation BM chimeras lacking MHC class II expression specifically on B cells indicated that nonspecific Ab production is independent of IL-6 or IFN-γ, and dependent on cognate CD4+ T cell help. Several observations were consistent with polyclonal B cell activation by γHV68, including the induction of durable serum levels of IgG reactive with mammalian dsDNA and murine type II collagen. Our findings indicate new directions for studies of this valuable model of γ-herpesvirus pathogenesis.

Original languageEnglish (US)
Pages (from-to)1820-1828
Number of pages9
JournalJournal of Immunology
Volume164
Issue number4
DOIs
StatePublished - Feb 15 2000

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B-Lymphocytes
Viruses
Cell Count
Bone Marrow
T-Lymphocytes
CD40 Ligand
Collagen Type II
Herpesviridae
Serum
Respiratory System
Interleukin-6
Spleen
Immunoglobulin G
Lymph Nodes
Epithelial Cells
Macrophages
Radiation
Cytokines
Infection

All Science Journal Classification (ASJC) codes

  • Immunology

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Analysis of the virus-specific and nonspecific B cell response to a persistent B-lymphotropic gammaherpesvirus. / Sangster, Mark Y.; Topham, David J.; D'Costa, Sybil; Cardin, Rhonda D.; Marion, Tony; Myers, Linda; Doherty, Peter C.

In: Journal of Immunology, Vol. 164, No. 4, 15.02.2000, p. 1820-1828.

Research output: Contribution to journalArticle

Sangster, Mark Y. ; Topham, David J. ; D'Costa, Sybil ; Cardin, Rhonda D. ; Marion, Tony ; Myers, Linda ; Doherty, Peter C. / Analysis of the virus-specific and nonspecific B cell response to a persistent B-lymphotropic gammaherpesvirus. In: Journal of Immunology. 2000 ; Vol. 164, No. 4. pp. 1820-1828.
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