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Influence of non-major histocompatibility complex differences on the severity of lymphocytic choriomeningitis
1Department of Experimental Pathology, John Curtin School of Medical Research, Canberra, ACT, Australia.
Abstract:
The role of the non-major histocompatibility complex (MHC) genetic background in the development of lymphocytic choriomeningitis (LCM) was examined for a range of mouse strains of the H-2k haplotype. The onset of meningitis relative to the time of injection of LCM virus was delayed and the maximal level of cellular extravasation into cerebrospinal fluid was lower in C3H/HeJ and CBA/H compared with AKR/J, B10.Br and BALB/c.H-2k mice. Adoptive transfer experiments indicated that the C3H mice are genuine low responders, but immune spleen cells from the CBA/H were as potent on a cell-for-cell basis as those from the AKR/J. Further analysis with CBA/H, AKR/J and (CBA/H x AKR/J)F1 mice showed that the pattern of high response for the AKR/J was dominant, with the differential kinetics of the development of meningitis correlating with the cellularity of the cervical lymph nodes. Thus, the generation of the LCM inflammatory process is not dictated solely by the MHC phenotype.
Insights
The non-major histocompatibility complex (MHC) genetic background influences lymphocytic choriomeningitis (LCM) severity. Mouse strain genetics, beyond MHC, dictate the inflammatory response to LCM virus.
Area of Science:
- Immunology
- Virology
- Genetics
Background:
- The major histocompatibility complex (MHC) is crucial for immune responses.
- Its role in lymphocytic choriomeningitis (LCM) development is well-studied.
- However, the influence of non-MHC genetic factors remains less understood.
Purpose of the Study:
- To investigate the impact of non-MHC genetic background on LCM development.
- To compare LCM pathogenesis in different mouse strains with the H-2k haplotype.
- To elucidate the genetic underpinnings of inflammatory responses to LCM virus.
Main Methods:
- Utilized various mouse strains of the H-2k haplotype.
- Inoculated mice with LCM virus and monitored meningitis onset and severity.
- Performed adoptive transfer experiments using immune spleen cells.
- Analyzed cervical lymph node cellularity in different mouse crosses.
Main Results:
- Meningitis onset was delayed and cellular extravasation was lower in C3H/HeJ and CBA/H mice compared to AKR/J, B10.Br, and BALB/c.H-2k mice.
- C3H mice were identified as low responders, while CBA/H immune cells were potent, similar to AKR/J.
- The high-response phenotype of AKR/J mice was dominant in (CBA/H x AKR/J)F1 crosses.
- Differential meningitis development kinetics correlated with cervical lymph node cellularity.
Conclusions:
- Non-MHC genetic background significantly influences the development and severity of LCM.
- Immune cell potency and lymph node cellularity are key factors in LCM pathogenesis.
- The MHC phenotype alone does not solely dictate the inflammatory process in LCM.