Oligoclonality of serum immunoglobulin G antibody responses to Streptococcus pneumoniae capsular polysaccharide serotypes 6B, 14, and 23F

Abstract

Serum antibodies (Abs) specific for the capsular polysaccharides of Streptococcus pneumoniae provide protection against invasive pneumococcal disease. Previous studies indicate that Abs to pneumococcal polysaccharide (PPS) serotypes 1 and 6B have limited clonal diversity. To determine if restricted diversity was a feature common to other PPS specificities, we examined the light (L)-chain expression and isoelectric heterogeneity of type 6B, 14, and 23F Abs elicited in 15 adults following PPS vaccination. At the population level, both PPS-6B and PPS-14 Abs expressed and chains, although 6B Abs more frequently expressed chains lambda and 14 Abs more frequently expressed chains. In individual sera, Abs were generally skewed towards either or expression. 23F-specific Abs had predominantly chains. Isoelectric focusing analyses showed that sera contained one or at most a few immunoglobulin G Ab spectrotypes to all three respective capsular serotypes, a result indicative of oligoclonality. A sequence analysis of a purified PPS-14-specific Ab having a single spectrotype gave uniform amino-terminal sequences for both the heavy chain (V H III subgroup) and the L chain (III-A27 V region). From these results we conclude that within individual adults, serum Ab responses to PPS serotypes 6B, 14, and 23F derive from a small number of dominant B-cell clones, and consequently variable-region expression is probably individually limited as well. Oligoclonality appears to be a general characteristic of human PPS-specific Ab repertoires, and we suggest that this property could lead to individual differences in Ab fine specificity and/or functional activity against encapsulated pneumococci.

Polysaccharide vaccines as probes of antibody repertoires in man

“…Avidity analyses of infant responses following conjugate vaccination show that individual sera segregate into high and low avidity categories, depending upon which conjugate is used for vaccination (see below). These findings likely hold significance for understanding protection from disease since avidity functions as a determinant of anti-Hib PS antibody protective activities, Recendy, we showed that the properties of oligoclonality, avidity variation and the correlation between avidity and protective function are also properties of adult antibodies to pneumococcal PSs (29,35).…”

“…This fundamental property of restricted antibody heterogeneity has made the Hib PS repertoire tractable to molecular analysis, Oligoclonality may be a universal feattire of human anti-PS antibody repertoires. Human antibody responses to Group A streptococcal carbohydrate (26) and to pneumococal PS serotypes 3, 6B, ]4, and 23F are similarly restricted in their isoelectric heterogeneity (27)(28)(29),…”

Risk factors in HIV-1-infected patients developing repetitive bacterial infections: toxicological, clinical, specific antibody class responses, opsonophagocytosis and Fcγ RIIa polymorphism characteristics

“…HIV-1 positive controls (n = 33) P* Healthy controls (n = 27) P † Antibodies effect of opiates on the immune system but with inconclusive and sometimes conflicting results [47][48][49]. There are reports indicating that oligoclonality appears to be a general characteristic of human pneumococcal polysaccharide-specific antibody repertoires, and we suggest that a deletion of polysaccharide responsive B cell clones may be a direct harmful effect of pneumococcal polysaccharides leading to a poor response in the cases group of patients [50]. It is possible that specific B cell clones may have been deleted by recurrent infections, leading to a poor vaccine response in the cases group.…”

Natural human antibodies to pneumococcus have distinctive molecular characteristics and protect against pneumococcal disease

“…The IgM mAbs that we have described, although generated following PncPS immunization and selected on the basis of PncPS binding, had both structural and functional features that were distinct from class-switched PncPS binding mAbs [17,37], and were characteristic of natural germline encoded polyreactive antibody derived from the poorly characterized B-1-like B cell lineage which recognizes common conformational motifs on both self-and microbial structures [38]. The broad specificity of the IgM mAbs produced by the heterohybridomas suggests that the individual antigenic determinants that these antibodies recognize was likely to be different to those for previously identified PC-specific and PncPS serotype-specific mAbs and are likely to be conformational epitopes rather than a continuous primary sequence [39,40].…”