CLEAVAGE OF MEMBRANE-BOUND CD40 LIGAND IS NOT REQUIRED FOR INDUCING B-CELL PROLIFERATION AND DIFFERENTIATION

The phycical interaction between the B cell surface molecule CD40 and its ligand, CD40L, is known to be crucial in the development and maint enance 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 m embrane-bound human CD40L on human B cells, we generated an uncleavabl e CD40L cDNA deletion mutant. The activities of transfectants expressi ng either mutated or wild-type CD40L were then compared on human B cel ls. Both the soluble and the uncleavable membrane-bound CD40L were abl e to induce, in conjunction with interleukin-4, B cell proliferation a nd 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.