Diffusible suppressor factor from splenic macrophages in murine plasmacytoma
Abstract:
The immunosuppressive effect of splenic macrophages (M phi) in mice bearing plasmacytoma was previously shown to be mediated by a diffusible factor. This diffusible suppressor factor (DSF) was found to be non-dialysable and sensitive to heating to 56 degrees C and to the proteolytic action of trypsin. The suppressor factor could be removed from culture supernatants by binding to ligands that specifically bind to corresponding myeloma proteins. DSF from splenic suppressor M phi of mice bearing MOPC 315 was capable of binding dinitrophenyl L-lysine, and that from mice bearing MOPC 104E, dextran S. The suppressor factor apparently cross-reacted with anti-idiotypic antibody to the corresponding myeloma protein, but did not interact with anti-isotypic antibody to mouse immunoglobulins (Ig). A higher concentration of mouse Ig than that found in DSF preparations did not have a suppressive effect. Metabolic inhibitors for RNA and protein, but not DNA synthesis effectively blocked the production of DSF. These findings suggest that DSF is a non-Ig protein that may have a structural similarity to myeloma idiotype. Continuous RNA and protein synthesis is required for the elaboration of DSF by splenic suppressor M phi in cultures.
Insights
Splenic macrophages produce a diffusible suppressor factor (DSF) that inhibits immune responses in mice with plasmacytoma. This non-immunoglobulin protein is crucial for tumor progression and requires continuous synthesis.
Area of Science:
- Immunology
- Cancer Biology
- Cell Biology
Background:
- Splenic macrophages (M phi) in tumor-bearing mice exhibit immunosuppressive properties.
- This immunosuppression is mediated by a diffusible factor (DSF).
Purpose of the Study:
- To characterize the nature and production of the diffusible suppressor factor (DSF).
- To elucidate the molecular properties and synthesis requirements of DSF.
Main Methods:
- Biochemical analysis of DSF (non-dialyzable, heat-sensitive, trypsin-sensitive).
- Ligand binding assays using myeloma proteins and specific ligands (dinitrophenyl L-lysine, dextran S).
- Immunological assays with anti-idiotypic and anti-isotypic antibodies.
- Inhibition studies using metabolic inhibitors of RNA, protein, and DNA synthesis.
Main Results:
- DSF binds to ligands specific for corresponding myeloma proteins.
- DSF cross-reacts with anti-idiotypic antibodies but not anti-isotypic antibodies to mouse immunoglobulins (Ig).
- DSF production is blocked by inhibitors of RNA and protein synthesis, but not DNA synthesis, indicating it is a non-Ig protein.
Conclusions:
- DSF is a novel non-Ig protein produced by splenic suppressor M phi.
- DSF possesses structural similarities to myeloma idiotype.
- Continuous RNA and protein synthesis are essential for DSF elaboration by M phi.
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