Cleavage of membrane-bound CD40 ligand is not required for inducing B cell proliferation and differentiation.
The physical interaction between the B cell surface molecule CD40 and its ligand, CD40L, is known to be crucial in the development and maintenance of humoral immunity. Recently it has been shown that the CD40L is processed and that its soluble cleavage products are released into the extracellular environment. To study the functions of soluble and membrane-bound human CD40L on human B cells, we generated an uncleavable CD40L cDNA deletion mutant. The activities of transfectants expressing either mutated or wild-type CD40L were then compared on human B cells. Both the soluble and the uncleavable membrane-bound CD40L were able to induce, in conjunction with interleukin-4, B cell proliferation and IgE synthesis. Therefore, membrane-bound and soluble CD40L exhibit the same pattern of activities on B cells and membrane CD40L cleavage is not a prerequisite for its function.
Pietravalle
F
F
Glaxo Institute for Molecular Biology, Immunology Department, Geneva, Switzerland.
Lecoanet-Henchoz
S
S
Aubry
J P
JP
Elson
G
G
Bonnefoy
J Y
JY
Gauchat
J F
JF
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D001483:Base Sequence; D023201:CD40 Ligand; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D006801:Humans; D008024:Ligands; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D008969:Molecular Sequence Data; D017384:Sequence Deletion / Q000276:immunology; D012995:Solubility
D008024:Ligands; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D023201:CD40 Ligand