title: Progressive depletion of peripheral B lymphocytes in 4-1BB (CD137) ligand/I-Ealpha)-transgenic mice.
abstract: 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-Ealpha 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.
authors.affiliation: Department of Immunology, Mayo Graduate and Medical Schools, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: G
authors.initials: G
authors.lastname: Zhu
authors.forename: D B
authors.initials: DB
authors.lastname: Flies
authors.forename: K
authors.initials: K
authors.lastname: Tamada
authors.forename: Y
authors.initials: Y
authors.lastname: Sun
authors.forename: M
authors.initials: M
authors.lastname: Rodriguez
authors.forename: Y X
authors.initials: YX
authors.lastname: Fu
authors.forename: L
authors.initials: L
authors.lastname: Chen
mesh_terms: D053330:4-1BB Ligand; D000375:Aging / Q000276:immunology; D000818:Animals; D000917:Antibody Formation; D017951:Antigen Presentation; D015703:Antigens, CD; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D018076:DNA, Complementary / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000378:metabolism*; D066298:In Vitro Techniques; D008024:Ligands; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010641:Phenotype; D011401:Promoter Regions, Genetic; D017475:Receptors, Nerve Growth Factor / Q000235:genetics* / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics* / Q000378:metabolism*; D013154:Spleen / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism*
chemical_list: D053330:4-1BB Ligand; D015703:Antigens, CD; D018076:DNA, Complementary; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D008024:Ligands; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C505715:Tnfrsf9 protein, mouse; C505975:Tnfsf9 protein, mouse; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D014409:Tumor Necrosis Factor-alpha