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, short- and long-term proliferation, differentiation and enhanced tyrosine phosphorylation of proteins. In addition, germinal centre centrocytes are prevented from undergoing apoptosis by activation through CD40 and receptor for antigen. 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 with a family of cell-surface glycoproteins that includes the receptors for nerve growth factor and tumour necrosis factor. 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.
Armitage
R J
RJ
Department of Immunology, Immunex Research & Development Corporation, Seattle, Washington 98101.
Fanslow
W C
WC
Strockbine
L
L
Sato
T A
TA
Clifford
K N
KN
Macduff
B M
BM
Anderson
D M
DM
Gimpel
S D
SD
Davis-Smith
T
T
Maliszewski
C R
CR
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism*; D001402:B-Lymphocytes / Q000378:metabolism; D001483:Base Sequence; D019013:CD40 Antigens; D023201:CD40 Ligand; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism; D008024:Ligands; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D013601:T-Lymphocytes / Q000378:metabolism; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; D008024:Ligands; D008562:Membrane Glycoproteins; D023201:CD40 Ligand; D007073:Immunoglobulin E