THE ROLE OF B-LYMPHOCYTES IN EXPERIMENTAL HERPES-SIMPLEX VIRAL RETINITIS

The purpose of this study was to examine B cell participation in exper imental herpes simplex virus (HSV) retinitis. Passive immunization wit h anti-herpes antibody protects BALB/c mice from herpes simplex retini tis (HSR). Using anti-Mu antibody treatment, we modified the B cell po pulation of C.B-17 mice, normally resistant to HSR, in order to test t he hypothesis that such treatment would render them susceptible to HSR by impairing their early antibody response to anterior chamber (AC) i noculation with HSV. We analysed the effect of anti-Mu treatment on th eir susceptibility to HSR and then employed Polymerase Chain Reaction (PCR) and ELISA techniques to study the patterns of immunoglobulin gen e and protein expression, and the T-cell receptor alpha/beta (TCR alph a beta) gene expression after AC inoculation of HSV. Immunohistopathol ogic analysis revealed that 100% of the B cell deficient mice (B-) dev eloped contralateral retinitis following AC inoculation, confirming th e hypothesis that anti-Mu antibody treatment would convert HSR-resista nt mice into HSR-susceptible ones. Transfer of B cells from naive cong enic donor mice resulted in 67% of recipient B- mice developing contra lateral retinitis. Transfer of anti-HSV antibody conferred nearly comp lete protection, with only 11% of mice developing retinitis (P < 0.005 ). PCR and ELISA analysis showed that both untreated and B- C.B-17 mic e showed similar dynamic patterns of mRNA IgG isotype expression and o f anti-HSV IgG isotypic antibody response following AC inoculation. Th us, we were forced to reject the hypothesis that an impaired early ant ibody response is primarily responsible for the increased HSR suscepti bility seen in B- mice. In contrast, PCR analysis of TCR alpha/beta mR NA expression revealed dramatic differences between susceptible and re sistant mice, suggesting that TCR VP selection and usage may be a crit ical factor influencing HSR-sensitivity in this murine model, and that B cells (and immunoglobulin isotype) may play a role in TCR VP select ion and usage after ocular encounter with HSV.