Antiviral antibody-producing cells in parenchymatous organs during persistent virus infection

In mice persistently infected with lymphocytic choriomeningitis virus (LCMV), the parenchymatous organs contain infiltrates of mononuclear cells, the sizes and numbers of which vary between strains and become more numerous and extensive when the animals grow older. Histologically, these were found to possess a tissue-like structure, and by use of immunohistologic procedures they were shown to contain plasma cells secreting IgM and IgG. Cells of kidneys, livers, brains, and spleens of LCMV carrier mice were dispersed by digestion with trypsin, leukocytes were separated by density gradient centrifugation, and numbers of cells producing antibodies against LCMV were determined by use of a solid-phase immunoenzymatic technique. In all these organs, cells producing LCMV-specific IgM and IgG antibodies were demonstrated, the latter more numerous than the former. Their numbers correlated with numbers and extent of the lymphoid cell infiltrates. The blood of the same mice was essentially free of antiviral antibody-forming cell. The proportion of cells producing LCMV-specific antibodies to all cells producing Ig of any specificity varied between organs, being lowest in spleen, intermediate in liver and kidney, and highest in the brain, where in individual mice up to 90% of all active cells produced virus-specific antibodies. The LCMV carrier mouse should prove to be a useful animal model to investigate antibody production in parenchymatous organs during persistent virus infections.