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Pleiotropic effects of the CD30 ligand on CD30-expressing cells and lymphoma cell lines
H J Gruss1, N Boiani, D E Williams
1Immunex Research and Development Corp, Department of Biochemistry, Seattle, WA 98101.
Insights
The CD30 ligand influences various lymphoma cell lines, enhancing Ig secretion and proliferation in some, while inducing cell death in others. This suggests a role for CD30 signaling in lymphoma pathogenesis.
Area of Science:
- Immunology
- Cell Biology
- Oncology
Background:
- CD30 is a tumor necrosis factor receptor superfamily member.
- CD30 is a cell surface antigen found on Hodgkin's and Reed-Sternberg cells.
Purpose of the Study:
- To investigate the biological activities of recombinant human CD30 ligand on various CD30+ human lymphoma cell lines.
- To explore the potential pathophysiological role of the CD30-CD30 ligand interaction in lymphomas.
Main Methods:
- Expression of recombinant human CD30 ligand on CV-1/EBNA cells.
- Testing CD30 ligand's effects on Ig secretion, proliferation, and cell viability of different lymphoma cell lines.
- Utilizing new anti-CD30 antibodies (M44, M67) to assess biological activities.
Main Results:
- CD30 ligand enhanced Ig secretion in EBV-immortalized B-cell lines but not Burkitt lymphoma lines.
- Proliferation was enhanced in T-cell-like Hodgkin's disease lines and adult T-cell leukemia, but not in B-cell-like Hodgkin's lines or other CD30+ B-cell lines.
- CD30 ligand induced cytolytic cell death, reducing proliferation and viability in large-cell anaplastic lymphoma lines.
- Anti-CD30 antibodies M44 and M67 showed similar biological activities to the CD30 ligand.
Conclusions:
- The CD30 ligand exhibits pleiotropic biological activities on diverse CD30+ lymphoma cell lines.
- The CD30-CD30 ligand interaction may play a pathophysiological role in Hodgkin's lymphoma and certain non-Hodgkin's lymphomas.
Abstract:
CD30 is a member of the tumor necrosis factor receptor superfamily. CD30 was originally described as a cell surface antigen on primary and cultured Hodgkin's and Reed-Sternberg cells. In this study, recombinant human CD30 ligand was expressed on the surface of CV-1/EBNA cells and tested for biologic activities on a variety of different CD30+ human lymphoma cell lines. CD30 ligand enhanced Ig secretion of Epstein-Barr virus (EBV)-immortalized, CD30+ lymphoblastoid B-cell lines, but not Burkitt lymphoma lines. Recombinant CD30 ligand enhanced proliferation of "T-cell-like" Hodgkin's disease-derived cell lines and an adult T-cell leukemia cell line, but not "B-cell-like" Hodgkin's disease-derived cell lines, CD30+, EBV-immortalized lymphoblastoid B-cell lines, or CD30+ and EBV+ tumor B-cell non-Hodgkin's lymphoma cell lines. In addition, CD30 ligand mediated reduction of proliferation and viability, by induction of cytolytic cell death, of CD30+, large-cell anaplastic lymphoma cell lines. Two new antibodies, M44 and M67, against the CD30 antigen demonstrated similar biologic activities to the CD30 ligand. Taken together, these data demonstrate pleiotropic biologic activities of the CD30 ligand on different CD30+ lymphoma cell lines and indicate that the CD30-CD30 ligand interaction might have a pathophysiologic role in Hodgkin's and some non-Hodgkin's lymphomas.