Related Experiment Video
Updated: Aug 2, 2026
Isolation Protocol of Mouse Monocyte-derived Dendritic Cells and Their Subsequent In Vitro Activation with Tumor Immune Complexes
Published on: May 31, 2018
Immunomodulatory activity of monophosphoryl lipid A in C3H/HeJ and C3H/HeSnJ mice
J R Hiernaux1, P W Stashak, J L Cantrell
1Ribi ImmunoChem Research, Inc., Hamilton, Montana 59840.
Abstract:
Treatment with nontoxic monophosphoryl lipid A (MPL) derived from a polysaccharide-deficient, heptoseless Re mutant of either Salmonella typhimurium or Salmonella minnesota R595 enhanced the immunoglobulin M (IgM) anti-type III pneumococcal polysaccharide (SSS-III) antibody response of C3H/HeSnJ mice. Such an adjuvant effect was not observed in lipopolysaccharide-nonresponder C3H/HeJ mice. Nevertheless, C3H/HeJ spleen cells produced a weak mitogenic response to both preparations of MPL in vitro, and C3H/HeJ mice showed a significant increase in serum IgM levels without an increase in numbers of splenic IgM-secreting plaque-forming cells after in vivo treatment with MPL. A significant increase in serum IgG3 levels was accompanied by a transient decrease in serum IgG1 levels in C3H/HeSnJ mice given MPL; such non-antigen-specific polyclonal effects were not observed in C3H/HeJ or in athymic nu/nu mice. Since the enhanced antibody response to SSS-III has been attributed to the inactivation of suppressor T cells by MPL and since suppressor-T-cell activity is demonstrable in both C3H/HeSnJ and C3H/HeJ mice, these findings imply that (i) the suppressor T cells of C3H/HeJ mice are refractory to inactivation by MPL and (ii) some of the polyclonal and mitogenic effects produced in C3H/HeJ mice are due to the direct action of MPL on B lymphocytes.
Insights
Monophosphoryl lipid A (MPL) enhances antibody responses in certain mice by affecting T cells. However, MPL shows direct B cell effects in nonresponder mice, indicating varied immune system interactions.
Area of Science:
- Immunology
- Microbiology
Background:
- Nontoxic monophosphoryl lipid A (MPL) is derived from bacterial mutants.
- MPL's adjuvant effects on antibody production are well-documented.
Purpose of the Study:
- To investigate the differential effects of MPL on immune responses in C3H/HeSnJ and C3H/HeJ mice.
- To elucidate the mechanisms behind MPL's adjuvant activity and its interaction with different immune cell types.
Main Methods:
- Treatment of C3H/HeSnJ and C3H/HeJ mice with MPL.
- In vitro assessment of mitogenic responses in C3H/HeJ spleen cells.
- Measurement of serum immunoglobulin M (IgM) and IgG3 levels.
- Analysis of splenic IgM-secreting plaque-forming cells.
Main Results:
- MPL enhanced the IgM anti-type III pneumococcal polysaccharide (SSS-III) antibody response in C3H/HeSnJ mice but not in C3H/HeJ mice.
- C3H/HeJ mice showed increased serum IgM but not splenic IgM-secreting cells after MPL treatment.
- MPL induced polyclonal effects, including increased IgG3 and decreased IgG1, in C3H/HeSnJ mice, which were absent in C3H/HeJ mice.
Conclusions:
- Suppressor T cells in C3H/HeJ mice are resistant to MPL-induced inactivation.
- MPL exerts direct mitogenic effects on B lymphocytes in C3H/HeJ mice.
- MPL's adjuvant effects are dependent on the responder status of the host immune system.
