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*
Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN, 38105; and Departments of
Microbiology and Immunology, and
Pediatrics, University of Tennessee, Memphis, TN 38163
Respiratory challenge of mice with murine gammaherpesvirus 68
(
HV68) results in acute replication in respiratory epithelial cells
and persistent, latent infection of B cells and macrophages. HV68
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-, and dependent on
cognate CD4+ T cell help. Several observations were
consistent with polyclonal B cell activation by HV68, 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 -herpesvirus
pathogenesis.
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