The human T cell antigen gp39, a member of the TNF gene family, is a ligand for the CD40 receptor: expression of a soluble form of gp39 with B cell co-stimulatory activity

EMBO J. 1992 Dec;11(12):4313-21.

Abstract

Signals delivered to B cells via CD40 can synergize with those provided by other B cell surface receptors to induce B cell proliferation and antibody class switching as well as modulate cytokine production and cell adhesion. Recently, it has been shown that the ligand for CD40 is a cell surface protein of approximately 39 kDa expressed by activated T cells, gp39. Here we report on the isolation and characterization of a cDNA clone encoding human gp39, a type II membrane protein with homology to TNF, and the construction and characterization of a soluble recombinant form of gp39. COS cell transfectants expressing gp39 synergized with either anti-CD20 mAb or PMA to drive strong B cell proliferation and alone were able to drive B cells to proliferate weakly. In all cases the B cell proliferation induced by gp39-expressing COS cells was reduced to background levels by the addition of soluble CD40. Unlike gp39-expressing COS cells, recombinant soluble gp39 was not mitogenic alone and required co-stimulation to drive B cell proliferation. These results suggest that B cells require a second signal besides gp39-CD40 to drive proliferation and that soluble gp39 alone in a non-membrane bound form is able to provide co-stimulatory signals to B cells.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Antigens, CD / metabolism*
  • Antigens, Differentiation, B-Lymphocyte / metabolism*
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology
  • Base Sequence
  • CD40 Antigens
  • CD40 Ligand
  • Cell Division
  • Cell Line
  • Cells, Cultured
  • DNA
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Molecular Sequence Data
  • Multigene Family
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Sequence Homology, Amino Acid
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Tumor Necrosis Factor-alpha / genetics*

Substances

  • Antigens, CD
  • Antigens, Differentiation, B-Lymphocyte
  • CD40 Antigens
  • Membrane Proteins
  • Recombinant Fusion Proteins
  • Tumor Necrosis Factor-alpha
  • CD40 Ligand
  • DNA

Associated data

  • GENBANK/M95796
  • GENBANK/M95797
  • GENBANK/M95798
  • GENBANK/X66364
  • GENBANK/X66365
  • GENBANK/X67872
  • GENBANK/X67873
  • GENBANK/Z14954
  • GENBANK/Z14955
  • GENBANK/Z15017