Functional CD40 ligand expressed by human blood dendritic cells is up-regulated by CD40 ligation.
We examined whether human blood dendritic cells (DCs) express a functional ligand for CD40 (CD40L). Human blood DCs expressed significant amounts of cell surface CD40L identical to that expressed on activated T cells, as detected by mAb to CD40L or a chimeric CD40.Ig fusion protein (CD40.Ig). Stimulation through CD40 up-regulated protein and mRNA CD40L expression in DCs, B cells, and B cell lines. CD40-mediated CD40L expression was inhibited by a protein tyrosine kinase inhibitor, herbimycin, in a dose-dependent manner, suggesting that the induction of CD40L expression via CD40 requires protein tyrosine kinase activity. CD40L surface expression correlated with constitutive or inducible levels of CD40L-specific mRNA, as determined by reverse transcribed PCR analysis (RT-PCR) using CD40L-homologous primers. Furthermore, CD40L on DCs was functional, since CD40L+ DCs, unlike CD40L- DCs, induced B cell IgG and IgA production, and this induction could be inhibited by blocking CD40L-CD40 interactions with mAb to CD40L. Thus, CD40L on DCs and CD40L induced by crosslinking CD40 may regulate B cell activation and maturation. The importance of DC CD40L expression on B cell function is discussed.
Pinchuk
L M
LM
Regional Primate Research Center, University of Washington Medical Center, Seattle 98195, USA.
Klaus
S J
SJ
Magaletti
D M
DM
Pinchuk
G V
GV
Norsen
J P
JP
Clark
E A
EA
D001402:B-Lymphocytes / Q000378:metabolism; D002051:Burkitt Lymphoma; D019013:CD40 Antigens / Q000096:biosynthesis / Q000378:metabolism*; D023201:CD40 Ligand; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D008024:Ligands; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D014066:Palatine Tonsil / Q000166:cytology; D016133:Polymerase Chain Reaction; D011485:Protein Binding / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000276:immunology*
D019013:CD40 Antigens; D008024:Ligands; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D023201:CD40 Ligand