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

Respiratory challenge of mice with murine gammaherpesvirus 68 (gamma HV68) results in acute replication in respiratory epithelial cells and persistent , latent infection of B cells and macrophages. gamma HV68 elicits virus-spe cific Ab, and also nonspecifically activates B cells to Ab production throu gh a CD4(+) T cell dependent process. The current analysis characterizes vi rus-specific and nonspecific Ab production at the single cell level and inv estigates the requirements and nature of the nonspecific response. Virus-sp ecific 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 n umbers 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 i sotypes predominated. Analysis of cytokine-deficient mice, CD40 ligand-defi cient mice, and radiation BM chimeras lacking MHC class II expression speci fically on B cells indicated that nonspecific Ab production is independent of IL-6 or IFN-gamma, and dependent on cognate CD4(+) T cell help. Several observations were consistent with polyclonal B cell activation by gamma HV6 8, including the induction of durable serum levels of IgG reactive with mam malian dsDNA and murine type II collagen, Our findings indicate new directi ons for studies of this valuable model of gamma-herpesvirus pathogenesis.