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Interference between Neisseria meningitidis and PC-KLH induced anti-phosphorylcholine PFC responses in NZB/W
1Departamento de Microbiología y Parasitología, Universidad de Santiago de Compostela, España.
Abstract:
In this work, we demonstrate that the simultaneous injection of PC-KLH and Neisseria meningitidis-derived antigens [NMB or PC-(NMB)HI] induced in old NZB/W mice defective responses as does PC-KLH challenge. On the other hand, the simultaneous injection of both immunogenic preparations of N. meningitidis evoked responses similar to those shown by old mice challenged with NMB alone. Alteration in PC-specific PFC responses also affected hapten-free inhibition profiles and their heterogeneities. The increase in PC50s of anti-phosphorylcholine PFC responses and their heterogeneities induced by certain antigens with aging is correlated with a decrease in T15 idiotype expression, suggesting that after the T15 dominant clone disappears no other clone takes control of the anti-PC response. These results suggest that the mechanism(s) involved in the regulation of T15 marker expression play an important role in the inability of old NZB/W mice to mount good anti-PC responses and suggest that regulatory mechanisms induced by PC-KLH dominate those elicited by NMB.
Insights
Simultaneous injection of PC-KLH and Neisseria meningitidis antigens impairs immune responses in aging mice. Regulatory mechanisms induced by PC-KLH dominate, impacting anti-phosphorylcholine antibody production and T15 idiotype expression.
Area of Science:
- Immunology
- Aging Research
- Vaccinology
Background:
- Aging impairs immune responses, particularly antibody production.
- The T15 idiotype is crucial for anti-phosphorylcholine (anti-PC) antibody responses.
- NZB/W mice are a model for studying age-related immune dysfunction.
Purpose of the Study:
- To investigate the impact of simultaneous antigen injections on immune responses in aged NZB/W mice.
- To explore the role of PC-KLH and Neisseria meningitidis antigens in modulating anti-PC antibody production.
- To understand the relationship between T15 idiotype expression and immune response heterogeneity with aging.
Main Methods:
- Simultaneous injection of PC-KLH and N. meningitidis-derived antigens (NMB or PC-(NMB)HI) into aged NZB/W mice.
- Assessment of PC-specific plaque-forming cell (PFC) responses.
- Analysis of hapten-free inhibition profiles and heterogeneities.
- Evaluation of T15 idiotype expression in anti-PC PFC responses.
Main Results:
- Simultaneous PC-KLH and N. meningitidis antigen injection induced defective immune responses, similar to PC-KLH alone.
- Responses to simultaneous N. meningitidis antigens resembled those from NMB challenge alone.
- Alterations in PC-specific PFC responses affected hapten-free inhibition profiles.
- Increased PC50s and heterogeneity in anti-PC PFC responses correlated with decreased T15 idiotype expression.
Conclusions:
- Regulatory mechanisms induced by PC-KLH dominate over those elicited by N. meningitidis.
- The disappearance of the T15 dominant clone, without subsequent clonal takeover, contributes to impaired anti-PC responses in aging.
- T15 marker expression regulation is critical for mounting effective anti-PC responses in aged NZB/W mice.