ANALYSIS OF T-CELL RECEPTOR V-BETA GENE-EXPRESSION IN B-CELL DEFICIENT MICE AFTER EXPERIMENTAL HERPES-SIMPLEX VIRUS KERATITIS

To examine the importance of B cells in the regulation of the T cell r esponse to herpes simplex virus (HSV) infection, we have analyzed the selection of the T cell receptor (TCR) repertoire in C.B-17 mice that lack B cells (B-mice) compared with age-matched immunocompetent C.B-17 mice, usually resistant to herpes simplex keratitis (HSK). TCR VP tra nscripts used by these mice were analyzed by polymerase chain reaction (PCR) with variable gene-specific primers. Clinical examination showe d that the incidence of HSK was significantly different between untrea ted (control) and anti-mu antibody (Ab)-treated mice (p <0.0001). Pass ive transfer of anti-HSV Ab into B-mice, before infection, prevented H SK; transfer of naive B cells allowed HSK to evolve in 50% of these mi ce. At the level of gene expression, we demonstrated that the anti-mu Ab treatment altered TCR VP gene expression in eyes, spleen, thymus an d lymph nodes (LN) of C.B-17 mice. Preferential utilization of a singl eTCR Tb gene was not detected in the course of the disease except in L N, although in resistant mice there were different patterns of mRNA in duction in T cells expressing specific TCR Vb elements that were not s een in susceptible mice, namely the lack of expression of V beta 8.1, V beta 8.2 and V beta 8.3 in eyes, the expression of V beta 7 in splee n, and the lack expression of V beta 6 and V beta 13 in thymus. These observations together with previous findings suggest that at the level of protein production, anti-HSV Ab not only can provide protection ag ainst HSK but is also a critical component for protection against HSV in normally resistant C.B17 mice, and that a dysregulation of the immu ne system in B- mice is manifested by dramatic changes in TCR V beta u sage at the molecular level.