Regulation of human B cell function by recombinant CD40 ligand and other TNF-related ligands.
To assess the potential of CD40 ligand (CD40L) and the related molecules CD27 ligand (CD27), CD30 ligand (CD30L), and membrane TNF-alpha to stimulate B cell responses, expression of these proteins in the baculovirus system was performed. Sf9 cells expressing these membrane molecules were cultured with normal human B cells and a variety of B cell lines to assess the functional outcome. The signal provided by CD40L promotes aggregation of B cells, stimulates vigorous proliferation, and induces germ-line transcription of downstream heavy chain constant region genes in the absence of cytokine costimulation. In contrast, CD27L, CD30L, and TNF-alpha had no effects on B cell proliferation. CD27L and TNF-alpha had no effect on the induction of germ-line transcripts, whereas CD30L consistently inhibited constitutive and CD40L-induced germ-line transcription of the epsilon gene by B cell lines that express CD30. These results demonstrate the various members of the TNF family exert specific effects on human B cell function, with CD40L and CD30L providing powerful, but opposing, effects on l epsilon transcription.
Jumper
M D
MD
University of Texas Southwestern Medical Center at Dallas, Simmons Arthritis Research Center 75235, USA.
Nishioka
Y
Y
Davis
L S
LS
Lipsky
P E
PE
Meek
K
K
D015703:Antigens, CD / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects / Q000502:physiology*; D001483:Base Sequence; D053282:CD27 Ligand; D053285:CD30 Ligand; D023201:CD40 Ligand; D005822:Genetic Vectors; D000949:Histocompatibility Antigens Class II; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D008565:Membrane Proteins / Q000494:pharmacology; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D015703:Antigens, CD; D053282:CD27 Ligand; D053285:CD30 Ligand; C505771:CD70 protein, human; D000949:Histocompatibility Antigens Class II; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011994:Recombinant Proteins; C505774:TNFSF8 protein, human; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand