Progressive depletion of peripheral B lymphocytes in 4-1BB (CD137) ligand/I-Ealpha)-transgenic mice

J Immunol. 2001 Sep 1;167(5):2671-6. doi: 10.4049/jimmunol.167.5.2671.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 4-1BB Ligand
  • Aging / immunology
  • Animals
  • Antibody Formation
  • Antigen Presentation
  • Antigens, CD
  • B-Lymphocytes / immunology*
  • Base Sequence
  • DNA, Complementary / genetics
  • Histocompatibility Antigens Class II / genetics*
  • Histocompatibility Antigens Class II / metabolism*
  • In Vitro Techniques
  • Ligands
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Phenotype
  • Promoter Regions, Genetic
  • Receptors, Nerve Growth Factor / genetics*
  • Receptors, Nerve Growth Factor / metabolism*
  • Receptors, Tumor Necrosis Factor / genetics*
  • Receptors, Tumor Necrosis Factor / metabolism*
  • Spleen / immunology
  • Spleen / pathology
  • T-Lymphocytes / immunology
  • Tumor Necrosis Factor Receptor Superfamily, Member 9
  • Tumor Necrosis Factor-alpha / genetics*
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • 4-1BB Ligand
  • Antigens, CD
  • DNA, Complementary
  • Histocompatibility Antigens Class II
  • I-E-antigen
  • Ligands
  • Receptors, Nerve Growth Factor
  • Receptors, Tumor Necrosis Factor
  • Tnfrsf9 protein, mouse
  • Tnfsf9 protein, mouse
  • Tumor Necrosis Factor Receptor Superfamily, Member 9
  • Tumor Necrosis Factor-alpha