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The influence of monophosphoryl lipid A (MPL) on erythrocyte autoantibody formation
T Hraba1, P J Baker, C E Taylor
1Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Twinbrook-II Research Facility, Rockville, MD.
Abstract:
The onset and the amount of erythrocyte autoantibodies induced by the injection of C57BL/6N mice with rat red blood cells (RRBC) were hastened and increased, respectively, after the administration of monophosphoryl lipid A (MPL); this was not the case for similarly treated BALB/cAnN mice, which make a lower autoantibody response after immunization with RRBC. The transfer of spleen cells from donor C57BL/6N mice immunized with RRBC suppressed autoantibody formation in recipient mice subsequently immunized with RRBC; however, treatment with MPL prevented neither the induction nor the expression of such suppression. This suggests that the increased autoantibody response in RRBC-immunized C57BL/6N mice treated with MPL is not due to the inactivation of suppressor cell activity which, in other studies, was found to be extremely sensitive to MPL.
Insights
Monophosphoryl lipid A (MPL) enhances erythrocyte autoantibody production in C57BL/6N mice but not BALB/cAnN mice. MPL did not affect suppressor cell activity, suggesting a different mechanism for the enhanced autoantibody response.
Area of Science:
- Immunology
- Autoimmunity
- Adjuvant research
Background:
- Erythrocyte autoantibodies can be induced by immunization with foreign red blood cells.
- Monophosphoryl lipid A (MPL) is an adjuvant known to modulate immune responses.
- Genetic background influences autoantibody production and immune responses to adjuvants.
Purpose of the Study:
- To investigate the effect of MPL on autoantibody production in different mouse strains.
- To determine if MPL influences suppressor cell activity in the context of autoantibody formation.
Main Methods:
- Immunization of C57BL/6N and BALB/cAnN mice with rat red blood cells (RRBC).
- Administration of monophosphoryl lipid A (MPL) to a subset of mice.
- Spleen cell transfer experiments from immunized donors to naive recipients.
- Assessment of erythrocyte autoantibody levels and suppressor cell activity.
Main Results:
- MPL administration hastened and increased erythrocyte autoantibody levels in C57BL/6N mice immunized with RRBC.
- MPL did not significantly alter the autoantibody response in similarly treated BALB/cAnN mice.
- Transfer of spleen cells from RRBC-immunized C57BL/6N mice suppressed autoantibody formation in recipients.
- MPL treatment did not prevent the induction or expression of this suppressor cell-mediated suppression.
Conclusions:
- The enhanced autoantibody response in MPL-treated C57BL/6N mice is not mediated by the inactivation of suppressor cell activity.
- MPL's adjuvant effect on autoantibody production in this model may involve mechanisms independent of suppressor cell modulation.
- Mouse strain genetic background significantly impacts the response to MPL and autoantigen challenge.