A negative regulatory function of B7 revealed in B7-1 transgenic mice.
To analyze the functions of T cell costimulators in vivo, we have constructed a transgenic mouse strain that constitutively expresses murine B7-1 on mature B cells. Antibody responses to T-dependent hapten-protein conjugates and serum immunoglobulin levels are markedly depressed in B7-1 transgenic mice. This immune deficiency is not due to an intrinsic B cell defect, as antibody responses to T-independent hapten conjugates are normal. Furthermore, treatment with anti-B7-1 restores the capacity of transgenic mice to respond to hapten-protein conjugates, demonstrating that the deficient antibody responses are directly attributable to the expression of B7-1. These results suggest that the temporally regulated expression of costimulators such as B7-1 may contribute to either initiation or down-regulation (feedback inhibition) of T-dependent immune responses in vivo, and that the inhibitory function is dominant in transgenic mice that constitutively express high levels of this costimulator.
Sethna
M P
MP
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
van Parijs
L
L
Sharpe
A H
AH
Abbas
A K
AK
Freeman
G J
GJ
D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology; D018122:B7-1 Antigen / Q000235:genetics / Q000502:physiology*; D001483:Base Sequence; D015870:Gene Expression; D051379:Mice; D008822:Mice, Transgenic / Q000276:immunology*; D008969:Molecular Sequence Data
D018122:B7-1 Antigen