Immunoresponses to Neisseria meningitidis epitopes: suppression of secondary response to phosphorylcholine is carrier specific
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Abstract:
Results of our previous work have shown that Neisseria meningitidis serogroup B M986 can induce a phosphorylcholine (PC)-specific plaque-forming cell immunoresponse in mice. Also, a single injection of a relatively low dose of meningococci in NBF1 female mice induced a priming time-dependent suppression on subsequent meningococcus challenge. This suppression was not due to switching to another class of immunoglobulin nor to the presence of a capsule on N. meningitidis. In this study we show that suppression induced by meningococcus is carrier specific. Furthermore, we offer evidence suggesting that the structure(s) on meningococcus that trigger this suppression is heat labile and different from the antigenic structure(s) recognized by the suppressed B cells. In addition, we found that there is a gradual increase in antibody secretion rates of N. meningitidis-induced anti-PC plaque-forming cells that correlates with N. meningitidis priming time. Rather unexpected was the fact that pretreatment of mice with PC-keyhole limpet hemocyanin (thymus-dependent antigen) had a great influence on the subsequent PC-specific immunoresponses induced by N. meningitidis and PC-coupled heat-inactivated meningococcus [PC-(NMB)HI], as shown by (i) a striking decrease in T15 idiotype expression, (ii) concomitant direct anti-PC plaque-forming cells reduction, (iii) switching to immunoglobulin G (N. meningitidis-induced immunoresponse) or immunoglobulin G plus immunoglobulin A [PC-(NMB)HI-induced immunoresponse], and (iv) a significant increase in heterogeneity of plaque-forming cell secretion rates. The possibility that N. meningitidis, PC-(NMB)HI, and PC-KLH stimulate B lymphocytes pertaining to three different subpopulations embedded in distinct regulatory circuits is discussed, with emphasis on the interrelationships between T-dependent and T-independent lymphocyte compartments. We focus on the possibility of the existence of high-level regulatory circuits in which lymphocyte subpopulations or sets of lymphocyte subpopulations with different requirements of activation are connected.
Insights
Neisseria meningitidis serogroup B can suppress immune responses. This suppression is carrier-specific and involves heat-labile structures, distinct from those triggering antibody production against phosphorylcholine (PC).
Area of Science:
- Immunology
- Microbial Pathogenesis
- Vaccine Development
Background:
- Previous studies demonstrated that Neisseria meningitidis serogroup B (NMB) can induce a phosphorylcholine (PC)-specific immunoresponse and suppress subsequent challenges in mice.
- The observed suppression was not attributed to immunoglobulin class switching or the presence of a capsule on N. meningitidis.
Purpose of the Study:
- To investigate the carrier specificity of NMB-induced immune suppression.
- To identify the nature of the NMB structure responsible for suppression.
- To analyze the impact of thymus-dependent antigens on PC-specific immune responses.
Main Methods:
- Mice were pretreated with N. meningitidis or PC-keyhole limpet hemocyanin (PC-KLH).
- Subsequent immune responses to NMB and PC-coupled heat-inactivated meningococcus [PC-(NMB)HI] were analyzed.
- Measurements included T15 idiotype expression, plaque-forming cell counts, immunoglobulin class switching, and antibody secretion rates.
Main Results:
- NMB-induced suppression was found to be carrier-specific.
- The suppressive structure on NMB is heat-labile and distinct from the PC-binding antigen.
- Pretreatment with PC-KLH significantly altered PC-specific responses, decreasing T15 idiotype and anti-PC cells, inducing immunoglobulin class switching, and increasing secretion rate heterogeneity.
Conclusions:
- N. meningitidis, PC-(NMB)HI, and PC-KLH may stimulate distinct B lymphocyte subpopulations within different regulatory circuits.
- Evidence suggests the existence of high-level regulatory circuits connecting lymphocyte subpopulations with varying activation requirements.
- Understanding these interactions is crucial for deciphering T-dependent and T-independent immune responses.