MOLECULAR AND BIOLOGICAL CHARACTERIZATION OF A MURINE LIGAND FOR CD40

THE CD40 surface molecule is a 277-amino-acid glycoprotein expressed on B lymphocytes, epithelial cells and some carcinoma cell lines. Monoclonal antibodies against CD40 mediate a variety of effects on B lymphocytes, including induction of intercellular adhesion 1,2, short- and long-term proliferation 3-5, differentiation 6,7 and enhanced tyrosine phosphorylation of proteins 8. In addition, germinal centre centrocytes are prevented from undergoing apoptosis by activation through CD40 and receptor for antigen 9. These data indicate that CD40 could be a receptor for an unknown ligand with important functions in B-cell development and activation. This hypothesis is strengthened by the homology of the extracellular region of the CD40 molecule 10 with a family of cell-surface glycoproteins 11,12 that includes the receptors for nerve growth factor 13,14 and tumour necrosis factor 11,15,16. Here we report the cloning of a ligand for CD40 that is expressed on the cell surface of activated T cells and mediates B-cell proliferation in the absence of co-stimulus, as well as IgE production in the presence of interleukin-4.