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CD27 signals through PKC in human B cell lymphomas
1Laboratory of Molecular Immunoregulation, Division of Basic Science, SAIC Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, MD, USA.
Abstract:
Tumour necrosis factor receptor (TNFR) superfamily members play critical roles in the regulation of cell proliferation and death. One member of the TNFR superfamily, CD27, is unique because it is the only covalently linked homodimer in the family. CD27 and its cellular ligand, CD70, have been implicated in the regulation of T cell and B cell interactions that lead to cellular activation and regulation of immunoglobulin expression. Due to the unique nature of CD27, we chose to screen a number of B cell lymphoma cell lines for CD27 and CD70 expression and evaluate CD27 activation by antibody cross-linking. Two cell lines, HT and SU-4, showed greater cellular proliferation when CD27 was cross-lined and this correlated with increased PKC activation. Additionally, in the HT cell line cell surface expression of IgG was increased by CD27 cross-linking. Thus we have identified cellular systems for the study of CD27 signal transduction that will allow definition of the CD27 signal cascade of some B cell lymphomas.
Insights
Tumour necrosis factor receptor (TNFR) superfamily member CD27 and its ligand CD70 regulate B cell interactions. Cross-linking CD27 in lymphoma cells increased proliferation and PKC activation, offering systems to study CD27 signaling.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Tumor necrosis factor receptor (TNFR) superfamily members are crucial for cell proliferation and death.
- CD27 is a unique, covalently linked homodimer within the TNFR superfamily.
- CD27 and its ligand CD70 are involved in T and B cell interactions, activation, and immunoglobulin regulation.
Purpose of the Study:
- To screen B cell lymphoma cell lines for CD27 and CD70 expression.
- To evaluate CD27 activation through antibody cross-linking.
- To identify cellular systems for studying CD27 signal transduction in B cell lymphomas.
Main Methods:
- Screening of B cell lymphoma cell lines for CD27 and CD70 expression.
- Antibody cross-linking of CD27 to induce activation.
- Assessment of cellular proliferation, PKC activation, and cell surface IgG expression.
Main Results:
- Two cell lines, HT and SU-4, exhibited increased cellular proliferation upon CD27 cross-linking.
- This proliferation correlated with enhanced protein kinase C (PKC) activation.
- In the HT cell line, CD27 cross-linking led to increased cell surface IgG expression.
Conclusions:
- Identified HT and SU-4 cell lines as suitable systems for studying CD27 signal transduction.
- Demonstrated that CD27 activation can promote proliferation and modulate immunoglobulin expression in B cell lymphomas.
- Established a foundation for defining the CD27 signaling cascade in specific B cell lymphomas.