Variable immune response against a developmentally regulated self-antigen.

We studied the reactivity of T and B cells against a soluble form of the glycoprotein of vesicular stomatitis virus (VSV-G) which was expressed in a transgenic mouse (line 23) under the control of the hormone regulated beta-lactoglobulin promoter. Transgenic mice expressed VSV-G in the thymus, spleen, mammary gland and lung. VSV-G transcripts in the thymus varied with age, i.e., expression was high early in life and decreased with age. VSV-G transgenic mice immunized with recombinant vaccinia virus expressing VSV-G exhibited normal VSV-G-specific IgM levels, but a 30-fold reduction in IgG response, indicating functional VSV-G-specific B cell activity but impaired T helper cell responses. Interestingly, VSV-G-specific T helper cell activity was reduced only early (4-10 weeks) and late in life (>40 weeks) but was normal in between. Double transgenic mice expressing VSV-G and a VSV-G-specific TCR (line 23x7) demonstrated that TCR transgenic CD4(+) T cells were partially deleted in early life, but then gradually repopulated the periphery and remained constant. These findings suggest that in line 23 two different mechanisms regulated levels of the immune response: clonal reduction/deletion of VSV-G-specific T cells during early life followed by peripheral anergy at a later stage.