title: The role of B lymphocytes in experimental herpes simplex viral retinitis.
abstract: The purpose of this study was to examine B cell participation in experimental herpes simplex virus (HSV) retinitis. Passive immunization with anti-herpes antibody protects BALB/c mice from herpes simplex retinitis (HSR). Using anti-Mu antibody treatment, we modified the B cell population of C.B-17 mice, normally resistant to HSR, in order to test the hypothesis that such treatment would render them susceptible to HSR by impairing their early antibody response to anterior chamber (AC) inoculation with HSV. We analysed the effect of anti-Mu treatment on their susceptibility to HSR and then employed Polymerase Chain Reaction (PCR) and ELISA techniques to study the patterns of immunoglobulin gene and protein expression, and the T-cell receptor alpha/beta (TCR alpha/beta) gene expression after AC inoculation of HSV. Immunohistopathologic analysis revealed that 100% of the B cell deficient mice (B-) developed contralateral retinitis following AC inoculation, confirming the hypothesis that anti-Mu antibody treatment would convert HSR-resistant mice into HSR-susceptible ones. Transfer of B cells from naive congenic donor mice resulted in 67% of recipient B- mice developing contralateral retinitis. Transfer of anti-HSV antibody conferred nearly complete protection, with only 11% of mice developing retinitis (P < 0.005). PCR and ELISA analysis showed that both untreated and B- C.B-17 mice showed similar dynamic patterns of mRNA IgG isotype expression and of anti-HSV IgG isotypic antibody response following AC inoculation. Thus, we were forced to reject the hypothesis that an impaired early antibody response is primarily responsible for the increased HSR susceptibility seen in B- mice. In contrast, PCR analysis of TCR alpha/beta mRNA expression revealed dramatic differences between susceptible and resistant mice, suggesting that TCR V beta selection and usage may be a critical factor influencing HSR-sensitivity in this murine model, and that B cells (and immunoglobulin isotype) may play a role in TCR V beta selection and usage after ocular encounter with HSV.
authors.affiliation: Hilles Immunology, Laboratory, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston 02114.
authors.forename: V
authors.initials: V
authors.lastname: Arrunategui-Correa
authors.forename: J
authors.initials: J
authors.lastname: Dutt
authors.forename: C S
authors.initials: CS
authors.lastname: Foster
mesh_terms: D000818:Animals; D000867:Anterior Chamber; D000914:Antibodies, Viral / Q000008:administration & dosage / Q000096:biosynthesis / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000637:transplantation; D001483:Base Sequence; D002455:Cell Division; D017931:DNA Primers; D005260:Female; D015870:Gene Expression; D006561:Herpes Simplex / Q000276:immunology*; D018259:Herpesvirus 1, Human / Q000276:immunology*; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000235:genetics; D016219:Immunotherapy, Adoptive; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D012173:Retinitis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology
chemical_list: D000914:Antibodies, Viral; D017931:DNA Primers; D007074:Immunoglobulin G; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell