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Updated: Aug 8, 2026

Generation of Human CD40-activated B cells
Published on: October 17, 2009
Cleavage of membrane-bound CD40 ligand is not required for inducing B cell proliferation and differentiation
F Pietravalle1, S Lecoanet-Henchoz, J P Aubry
1Glaxo Institute for Molecular Biology, Immunology Department, Geneva, Switzerland.
Insights
Soluble and membrane-bound CD40 ligand (CD40L) both stimulate B cell proliferation and IgE synthesis, indicating CD40L cleavage is not essential for its function in humoral immunity.
Area of Science:
- Immunology
- Molecular Biology
Background:
- The CD40-CD40L interaction is vital for humoral immunity.
- CD40L undergoes processing, releasing soluble forms into circulation.
Purpose of the Study:
- To investigate the functions of soluble and membrane-bound CD40L on human B cells.
- To determine if CD40L cleavage is necessary for its biological activity.
Main Methods:
- Generated an uncleavable CD40L cDNA deletion mutant.
- Compared activities of wild-type and mutant CD40L transfectants on human B cells.
Main Results:
- Both soluble and uncleavable membrane-bound CD40L induced B cell proliferation and IgE synthesis.
- These effects were observed in conjunction with interleukin-4.
Conclusions:
- Membrane-bound and soluble CD40L display similar functional activities on B cells.
- Cleavage of membrane-bound CD40L is not a prerequisite for its B cell-mediated functions.
Abstract:
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.
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