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Updated: Aug 1, 2026

Generation of Human CD40-activated B cells
Published on: October 16, 2009
Regulation of human B cell function by recombinant CD40 ligand and other TNF-related ligands
M D Jumper1, Y Nishioka, L S Davis
1University of Texas Southwestern Medical Center at Dallas, Simmons Arthritis Research Center 75235, USA.
Insights
CD40 ligand (CD40L) powerfully stimulates B cell proliferation and gene transcription. However, CD30 ligand (CD30L) inhibits this transcription, showing TNF family members have distinct impacts on B cell function.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- The Tumor Necrosis Factor (TNF) superfamily plays critical roles in immune regulation.
- Understanding the specific functions of TNF superfamily ligands in B cell responses is crucial for immunology research.
Purpose of the Study:
- To investigate the stimulatory potential of CD40 ligand (CD40L) and related molecules (CD27L, CD30L, TNF-alpha) on human B cell responses.
- To elucidate the distinct roles of these ligands in B cell proliferation and gene transcription.
Main Methods:
- Expression of CD40L, CD27L, CD30L, and TNF-alpha in the baculovirus system.
- Co-culture of Sf9 insect cells expressing these ligands with normal human B cells and B cell lines.
- Assessment of B cell aggregation, proliferation, and germ-line transcription.
Main Results:
- CD40L significantly promoted B cell aggregation, proliferation, and germ-line transcription without cytokine costimulation.
- CD27L, CD30L, and TNF-alpha did not affect B cell proliferation.
- CD30L inhibited germ-line transcription of the immunoglobulin epsilon gene in CD30-expressing B cells, while CD27L and TNF-alpha had no effect on germ-line transcripts.
Conclusions:
- Different TNF family members exert specific and sometimes opposing effects on human B cell function.
- CD40L is a potent stimulator of B cell responses, whereas CD30L can inhibit key transcriptional events.
Abstract:
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.
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