Immunoresponses to Neisseria meningitidis epitopes: suppression of secondary response to phosphorylcholine is carrier specific

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.

Interference between Neisseria meningitidis and PC‐KLH Induced Anti‐Phosphorylcholine PFC Responses in NZB/W Autoimmune Mice

“…If this is so, the simultaneous injection of PC-KLH plus another antigen able to elicit a good anti-PC response in aged mice might induce a normal response, because the other antigen would supply to B cells the appropriate activation signal. This experimental design had been previously used to study the mechanism underlying the suppression of anti-PC secondary response induced by NMB (8).…”

“…Moreover, responses induced in aged mice by coinjection of meningococcal antigens plus PC-KLH showed, in all cases, greater PC50, lower PFC numbers and lesser T15% and Hi values than those induced by the meningococcal antigen alone. On the contrary, when PC-KLH plus NMB were injected into NMB-primed mice, no interference was seen between both antigens and mice injected with the two antigens showed additive PFC responses (8), even more, the two antigens have additive responses when injected into untreated normal mice (25). As it would be very improbable that NMB enhanced PC-KLH responses without inducing any response itself, we think that the interpretation of a negative effect of PC-KLH on meningococcus responses, rather than the opposite explanation, i.e.…”

“…Each antigen was injected intravenously. PC50) a non-parametric method was used (4,8). The value of PC50 has been reported to be related to the secretion rate of antibody secreting cells rather than to the affinity or avidity of the antibody secreted (6).…”

“…Neisseria meningitidis group B as much other Gramnegative bacteria is a complex and particulate antigen able to elicit multiple immunomodulatory mechanisms at both molecular and cellular immunological level such as secretion of IgA proteases (22). Some antigenic preparations of N. meningitidis can induce a phosphorylcholine-specific response acting as a type 2 T-independent antigen (7) and can modulate this immunoresponse by causing carrier-specific suppression of the secondary response against natural and chemically bound meningococcal epitopes (7)(8)(9).…”

Protective immunity against Salmonella typhimurium elicited in mice by oral vaccination with phosphorylcholine encapsulated in poly(DL-lactide-co-glycolide) microspheres

“…Unlike the rabbit diarrhea model, oral experimental infection of mice by Salmonella typhimurium is a well-established model of intestinal invasive disease (29). This is of interest because we previously showed that after oral immunization with low doses of live S. typhimurium (30), a specific immune response to phosphorylcholine (PC), a ubiquitous antigen present on different pathogenic bacteria such as Streptococcus pneumoniae (2), S. typhimurium (30), Proteus morganii (11), and Neisseria meningitidis (17), could be induced in mice in both serum and intestinal secretions. Moreover, in mice infected by Streptococcus pneumoniae, anti-PC immunity proved protective against infection caused by this PC-bearing bacteria (6,7,36,37).…”