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 adhesion1,2, short- and long-term proliferation3–5, differentiation6,7 and enhanced tyrosine phosphorylation of proteins8. In addition, germinal centre centrocytes are prevented from undergoing apop-tosis by activation through CD40 and receptor for antigen9. 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 molecule10with a family of cell-surface glycoproteins11,12that includes the receptors for nerve growth factor13,14 and tumour necrosis factor11,15,16. 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 interIeukin-4.