Recombinant human CD40 ligand stimulates B cell proliferation and immunoglobulin E secretion

M K Spriggs1, R J Armitage, L Strockbine

  • 1Department of Molecular Biology, Immunex Research and Development Corporation, Seattle, Washington 98101.

Insights

Researchers identified the human CD40 ligand (hCD40-L), crucial for B cell proliferation and differentiation. This T cell-expressed molecule activates B cells, inducing immunoglobulin secretion, highlighting its role in immune responses.

Area of Science:

  • Immunology
  • Molecular Biology

Background:

  • CD40 signaling is vital for B lymphocyte proliferation and differentiation.
  • Previous identification of murine CD40 ligand (mCD40-L) with in vitro biological activity.

Purpose of the Study:

  • To isolate and characterize the human homologue of mCD40-L (hCD40-L).
  • To investigate the expression pattern and biological function of hCD40-L in B cell activation.

Main Methods:

  • Isolation of hCD40-L cDNA from activated peripheral blood T cells using crosshybridization.
  • Amino acid sequence prediction and comparison with mCD40-L.
  • Northern blot and FACS analysis for expression studies.
  • In vitro assays using transfected cells to assess B cell proliferation and immunoglobulin secretion.

Main Results:

  • hCD40-L is a 261 amino acid type II membrane protein with 78% amino acid identity to mCD40-L.
  • hCD40-L expression is restricted to T lymphocytes, predominantly on CD4+ T cells.
  • Transfected hCD40-L induced human B cell proliferation without costimuli.
  • hCD40-L, with IL-4, induced immunoglobulin E secretion from purified human B cells.

Conclusions:

  • The human CD40 ligand (hCD40-L) has been identified and characterized.
  • hCD40-L plays a significant role in T cell-mediated B cell activation, proliferation, and immunoglobulin secretion.
  • hCD40-L is a key mediator in immune responses involving B lymphocytes.