| Popis: |
RNA viruses are prevalent pathogens causing CNS infections worldwide. Animal models have shown that intrathecal humoral responses mediate protection and control of viral persistence, but there is limited knowledge about their local maintenance. In our model of murine coronavirus encephalomyelitis, virus-specific B cells begin to emerge in the inflamed CNS following T-cell mediated virus control, which coincides with germinal center (GC) formation in draining cervical lymph nodes (CLN). Further, peripheral GC formation is necessary for virus-specific B cells to infiltrate the CNS during chronic infection. We took advantage of transgenic reporter mice that mark GC-derived B cells and infected them with murine coronavirus strain A59 (MHV-A59) via intracranial injection. Our present data show that virus-specific B cells continue to migrate to areas of demyelination throughout the duration of GC reactions in the draining CLN. However, the peak migration period appears to be within days 14 to 21 p.i. and declines with decreasing GC reactivity. No evidence for local meningeal B-cell clusters suggests that protective B cells are partially maintained via ongoing recruitment. Newly migrated virus-specific B cells tend to equally lodge in both parenchymal and perivascular/meningeal spaces out to 4 weeks p.i. Starting week 5 p.i., when migration has already diminished, they are found preferentially in the meningeal spaces and to a lesser extent in the parenchyma and co-localize with CD4+ T cells. |
