4-1BB T-cell antigen binds to mature B cells and macrophages, and costimulates anti-mu-primed splenic B cells

Eur J Immunol. 1994 Feb;24(2):367-74. doi: 10.1002/eji.1830240215.


4-1BB is expressed on activated murine T cells and may function as an accessory signaling molecule during T-cell activation. To identify putative 4-1BB ligands, a fusion protein consisting of the extracellular domain of 4-1BB fused to human placental alkaline phosphatase (4-1BB-AP) was constructed. Alkaline phosphatase activity could then be used as an indicator of the relative amount of bound 4-1BB. These studies indicated that 4-1BB-AP specifically bound to the surface of various mature B and macrophage cell lines. 4-1BB-AP bound at low levels to T cell lines (non-activated and anti-CD3-activated), pre-B-cell lines, and an immature macrophage cell line. 4-1BB-AP did not bind to a glial tumor cell line, HeLa cells, or COS cells. In addition, 4-1BB-AP bound at higher levels to F(ab')2 anti-mu-activated primary B cells compared to anti-CD3-activated primary T cells. Scatchard analysis indicated that the A20 B cell lymphoma expressed 3680 binding sites per cell with a Kd of 1.86 nM. Affinity cross-linking studies demonstrated that a major cell surface species of 120 kDa bound to 4-1BB-AP; 4-1BB-AP also bound to a minor species of approximately 60 kDa. The addition of paraformaldehyde-fixed SF21 cells expressing recombinant 4-1BB synergized with F(ab')2 anti-mu in inducing splenic B cell proliferation suggesting that 4-1BB may function as a regulator of B cell growth.

Publication types

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

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology*
  • Antigens, CD
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Cell Communication
  • Female
  • Ligands
  • Lymphocyte Activation*
  • Lymphocyte Cooperation
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Receptors, Nerve Growth Factor / metabolism
  • Receptors, Tumor Necrosis Factor*
  • Recombinant Fusion Proteins
  • Spleen / cytology
  • T-Lymphocytes / immunology*
  • Tumor Necrosis Factor Receptor Superfamily, Member 9


  • Antigens, CD
  • Ligands
  • Receptors, Nerve Growth Factor
  • Receptors, Tumor Necrosis Factor
  • Recombinant Fusion Proteins
  • TNFRSF9 protein, human
  • Tnfrsf9 protein, mouse
  • Tumor Necrosis Factor Receptor Superfamily, Member 9