Conservation of biological properties of the CD40 ligand, CD154 in a non-mammalian vertebrate.
Signals delivered by the CD40 ligand, CD154, have crucial roles in immune responses in mammals, being required for development of germinal centres, maturation of T-dependent antibody responses, and generation of B-cell memory. To determine whether these functions were conserved in a non-mammalian species, a putative chicken CD 154 cDNA was used to make an oligomeric fusion protein, and to raise monoclonal antibodies. The antibodies detected surface expression on activated T-cells. The fusion protein detected expression of a receptor on B-cells, thrombocytes and macrophages. Biological effects of the fusion protein included induction of NO synthesis in a macrophage cell line, enhancement of splenic B-cell survival, and induction of apoptosis in a bursal lymphoma cell line. These observations demonstrated substantial functional equivalence with mammalian CD 154 and thus provided evidence for the early evolutionary emergence of the set of functions associated with this molecule, and its central role in the vertebrate immune system.
Tregaskes
Clive A
CA
Institute for Animal Health, Compton, Newbury, Berkshire RG20 7NN, UK.
Glansbeek
Harrie L
HL
Gill
Andrew C
AC
Hunt
Lawrence G
LG
Burnside
Joan
J
Young
John R
JR
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D023201:CD40 Ligand / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016827:CD8 Antigens / Q000235:genetics / Q000378:metabolism; D002417:Cattle; D002645:Chickens / Q000235:genetics / Q000378:metabolism*; D019143:Evolution, Molecular; D051379:Mice; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D000911:Antibodies, Monoclonal; D016827:CD8 Antigens; D011993:Recombinant Fusion Proteins; D023201:CD40 Ligand