A NEGATIVE REGULATORY FUNCTION OF B7 REVEALED IN B7-1 TRANSGENIC MICE

To analyze the functions of T cell costimulators in vivo, we have cons tructed a transgenic mouse strain that constitutively expresses murine B7-1 on mature B cells. Antibody responses to T-dependent hapten-prot ein conjugates and serum immunoglobulin levels are markedly depressed in B7-1 transgenic mice. This immune deficiency is not due to an intri nsic B cell defect, as antibody responses to T-independent hapten conj ugates are normal. Furthermore, treatment with anti-B7-1 restores the capacity of transgenic mice to respond to hapten-protein conjugates, d emonstrating that the deficient antibody responses are directly attrib utable to the expression of B7-1. These results suggest that the tempo rally regulated expression of costimulators such as B7-1 may contribut e to either initiation or down-regulation (feedback inhibition) of T-d ependent immune responses in vivo, and that the inhibitory function is dominant in transgenic mice that constitutively express high levels o f this costimulator.