Molecular and biological characterization of a murine ligand for CD40

Abstract

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 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 glycoproteins^11,12that 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 interIeukin-4.