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-Transgenic Mice1
Departments of
*
Immunology and
Neurology, Mayo Graduate and Medical Schools, Mayo Clinic, Rochester, MN 55905;
Department of Pathology, University of Chicago, Chicago, IL 60637; and
Shanghai International Cancer Institute and Eastern Hospital of Heptaobiliary Surgery, Shanghai, China
Interaction of 4-1BB (CD137) and its ligand (4-1BBL) is thought to
positively regulate cell-mediated and humoral immune responses. We have
prepared transgenic mouse strains that express 4-1BBL cDNA under the
control of MHC class II I-E
promoter. The 4-1BBL-transgenic mice
show progressive splenomegaly and selective depletion of
B220+ B cells accompanied with low levels of circulating
IgG and defective humoral responses to Ag challenge. In addition,
splenocytes from the transgenic mice fail to provide stimulation for
allogeneic T cells in both lymphoproliferative and CTL responses in
vitro, whereas their T cells remain functionally normal. Our results
reveal unexpected functions of 4-1BBL in the regulation of humoral
immune responses and Ag presentation.
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