Suppressor activity of splenic macrophages in murine plasmacytoma (PC) is inhibited by PC specific ligands
Abstract:
Spleens of BALB/c mice with plasmacytoma contain macrophages (M phi) which were found to suppress the in vitro immune function of normal splenic cells through a diffusible factor. The suppressor activity of these macrophages was reversibly inhibited by ligands specific for the corresponding PC globulin, but not by anti-idiotypic antibody. Anti-idiotypic antibody with complement, however, abrogated the suppressor function, presumably by cytotoxicity. Anti-isotype with complement was ineffective. These findings suggest binding of ligand to a surface receptor of the suppressor M phi that although clearly not PC globulin, may be structurally similar to the PC idiotype. These receptors are retained in 3 day cultures of macrophages and are not removed by intensive washing. Ligand binding appears to modulate the suppressor function of M phi through blocking of the production of diffusible suppressor factor.
Insights
Macrophages in mice with plasmacytoma suppress immune function via a diffusible factor. Ligand binding to macrophage receptors inhibits this suppressor activity, suggesting a potential therapeutic target for immune modulation.
Area of Science:
- Immunology
- Cell Biology
- Cancer Research
Background:
- Macrophages (M phi) in BALB/c mice with plasmacytoma exhibit immunosuppressive properties.
- These M phi secrete a diffusible factor that impairs the in vitro immune function of normal splenic cells.
Purpose of the Study:
- To investigate the mechanism by which M phi-mediated immunosuppression occurs.
- To identify potential targets for modulating M phi suppressor activity.
Main Methods:
- Culturing M phi from spleens of mice with plasmacytoma.
- Assessing M phi suppressor activity using in vitro immune function assays.
- Testing the effects of specific ligands and antibodies (anti-idiotypic, anti-isotype) with or without complement on M phi function.
Main Results:
- M phi suppressor activity was reversibly inhibited by ligands specific for PC globulin, but not by anti-idiotypic antibody alone.
- Anti-idiotypic antibody combined with complement abrogated M phi suppressor function, suggesting complement-dependent cytotoxicity.
- Anti-isotype antibodies with complement did not affect suppressor function.
- M phi suppressor receptors, distinct from PC globulin but potentially similar to PC idiotype, were identified and remained stable in culture.
Conclusions:
- Suppressor M phi possess surface receptors that bind specific ligands.
- Ligand binding modulates M phi suppressor function by blocking the production of diffusible suppressor factors.
- These findings suggest a novel mechanism for immune suppression in plasmacytoma and highlight potential therapeutic strategies targeting M phi receptors.
