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 response 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 V beta transcripts used by these mice were analyzed by polymerase chain reaction (PCR) with variable gene-specific primers. Clinical examination showed that the incidence of HSK was significantly different between untreated (control) and anti-mu antibody (Ab)-treated mice (p < 0.0001). Passive transfer of anti-HSV Ab into B. mice, before infection, prevented HSK; transfer of naive B cells allowed HSK to evolve in 50% of these mice. AT the level of gene expression, we demonstrated that the anti-mu Ab treatment altered TCR V beta gene expression in eyes, spleen, thymus and lymph nodes (LN) of C.B-17 mice. Preferential utilization of a single TCR Tb gene was not detected in the course of the disease except in LN, although in resistant mice there were different patterns of mRNA induction in T cells expressing specific TCR Vb elements that were not seen 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 spleen, 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 against HSK but is also a critical component for protection against HSV in normally resistant C.B17 mice, and that a dysregulation of the immune system in B. mice is manifested by dramatic changes in TCR V beta usage at the molecular level.