Variable immune response against a developmentally regulated self-antigen

We studied the reactivity of T and B cells against a soluble form of the gl ycoprotein of vesicular stomatitis virus (VSV-G) which was expressed in a t ransgenic mouse (line 23) under the control of the hormone regulated beta-l actoglobulin promoter. Transgenic mice expressed VSV-G in the thymus, splee n, mammary gland and lung. VSV-G transcripts in the thymus varied with age, i.e., expression was high early in life and deceased with age. VSV-G trans genic mice immunized with recombinant vaccinia virus expressing VSV-G exhib ited normal VSV-G-specific IgM levels, but a 30-fold reduction in IgG respo nse, indicating functional VSV-G-specific B cell activity but impaired T he lper cell responses. Interestingly, VSV-G-specific T helper cell activity w as reduced only early (4-10 weeks) and late in life (>40 weeks) but was nor mal in between. Double transgenic mice expressing VSV-C and a VSV-G-specifi c TCR (line 23 x 7) demonstrated that TCR transgenic CD4(+) T cells were pa rtially deleted in early life, but then gradually repopulated the periphery and remained constant. These findings suggest that in line 23 two differen t mechanisms regulated levels of the immune response: clonal reduction/dele tion of VSV-G-specific T cells during early life followed by peripheral ane rgy at a later stage. (C) 1999 Academic Press.