| Porcine reproductive and respiratory syndrome virus (PRRSV) is currently the most important pig pathogen worldwide and causes significant disease in young piglets. Much attention has been focused on anti-viral immune responses mounted by infected piglets, but how this virus directly impacts the piglet's immune system, in general, has largely been overlooked. Germfree (GF) isolator piglets secrete little immunoglobulin (Ig) over time, and cannot mount antigen (Ag)-specific antibody (Ab) responses upon immunization. What's more, their B-cell repertoires undergo little to no diversification, as measured by Ig VH gene usage. Bacterial colonization of the gastrointestinal tract of GF isolator piglets, however, stimulates humoral immunocompetence, resulting in increased Ig secretion, Ag-specific Ab responses and diversification of gut localized B-cells. To investigate how a virus might affect humoral immunocompetence and the B-cell repertoire, PRRSV infection studies were performed in GF isolator piglets.; PRRSV infection alone potently stimulated B-cells, resulting in hypergammaglobulinemia and infection-proximal lymphoid hyperplasia. Furthermore, infected piglets produced autoantibodies, IgG-containing serum immune complexes, and had IgM, IgG and IgA deposited in their kidneys. Aberrant B-cell responses observed after PRRSV infection were associated with a polyclonal B-cell repertoire that was not diversified. Consistent with potent B-cell stimulation, PRRSV-infected piglets produced higher titers of Ag-specific Ab after immunization, as compared to uninfected piglets. Consistent with non-specific polyclonal B-cell activation, PRRSV-infection induced dramatic Ab secretion from naive B-cells, i.e. in the absence of immunization, as compared to colonized-only piglets. The PRRSV-related effects on the B-cell compartment were not artifacts of the GF isolator piglet model since two other porcine viral infections did not induce similar symptoms.; These studies convincingly demonstrate that PRRSV infection uniquely induces polyclonal B-cell activation, immunopathology and little to no repertoire diversification. With the benefits that the isolator piglet affords immunological studies, i.e. exclusion of maternal and environmental variables, PRRSV infection could serve as a model for examining mechanisms involved in causing viral infection-mediated B-cell dysregulation. |
