Pathogenesis of herpes simplex virus-induced ocular immunoinflammatory lesions in B-cell-deficient mice

The role of B cells and humoral immunity in herpes simplex virus (HSV) ocul ar infections was studied in immunoglobulin IJ. chain gene-targeted B-cell- deficient mice (mu K/O), At doses of virus well tolerated by immunocompeten t mice, heightened susceptibility of mu K/O mice to herpetic encephalitis a s well as to herpetic stromal keratitis (HSK) was observed. An explanation was sought for the increased severity of HSK in the mu K/O mice. First, the lack of antibody responses in mu K/O mice resulted in longer viral persist ence and dissemination to the corneal stroma, the site of inflammation. Pro longed virus expression in the corneal stroma was suggested to cause bystan der activation of Th1-type CD4+ T cells, further contributing to the severi ty of HSK lesion expression in mu K/O mice, Second, mu K/O mice generated m inimal Th2 cytokine responses compared to wild-type mice, Such responses mi ght serve to downregulate the severity of Th1-mediated HSR lesions.