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CD40 ligation induces lymphotoxin alpha gene expression in human B cells
1Division of Immunology, Children's Hospital, Harvard Medical School, Boston, MA 02115.
International Immunology
|December 1, 1994
Summary
CD40 stimulation strongly increases membrane-bound lymphotoxin-alpha (LT-alpha) in B cells, suggesting a key role for this molecule in CD40-mediated B cell activation and immune responses.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- CD40 is crucial for T cell-dependent B cell proliferation and isotype switching.
- Tumor necrosis factor (TNF)-alpha and lymphotoxin (LT)-alpha are B cell-expressed cytokines involved in B cell activation.
Purpose of the Study:
- To investigate the expression of TNF-alpha and LT-alpha in human tonsillar B cells after anti-CD40 stimulation.
- To elucidate the role of CD40 ligation in regulating TNF-alpha and LT-alpha gene expression and protein presentation.
Main Methods:
- Human tonsillar B cells were stimulated with anti-CD40 monoclonal antibody (mAb).
- mRNA expression of TNF-alpha, LT-alpha, and LT-beta was analyzed.
- Protein expression and secretion of TNF-alpha and LT-alpha were assessed.
- The effect of IL-4 on anti-CD40-induced cytokine expression was evaluated.
Main Results:
- Anti-CD40 induced significant LT-alpha mRNA and membrane expression, but only weak TNF-alpha mRNA and minimal membrane TNF-alpha.
- CD40 ligation led to transcriptional activation of TNF-alpha and LT-alpha genes.
- Sustained membrane LT-alpha expression was observed for up to 120 hours post-stimulation.
- IL-4 augmented anti-CD40-induced LT-alpha mRNA and membrane expression.
Conclusions:
- CD40 ligation robustly induces membrane-bound LT-alpha expression in B cells.
- Membrane LT-alpha likely plays a significant role in CD40-mediated B cell activation processes.