Differences within Mono‐ and Dizygotic Twin‐Pairs in Spectrotypes and Clones of IgG2 Antibodies to Pneumococcal Polysaccharide Type 1 and C‐Polysaccharide After Vaccination

Abstract

Spectrotypes and clones of antibodies against pneumococcal capsular polysaccharide (Ps) type 1 and C-polysaccharide (C-Ps) were determined before and after immunization with a polyvalent pneumococcal Ps vaccine in 84 mono- or dizygotic twins. The method used was a micromodification of a rapid isoelectric focusing-affinity (IEF-affinity) immunoblot technique in agarose permitting characterization of isotype, light chain and Gm type. After vaccination the anti-type 1 Ps + anti-C-Ps clones were different in 75% of the monozygotic and 79% of the dizygotic twins. The anti-type 1 Ps clones differed among 72% of the monozygotic and 85% of the dizygotic twins (P > 0.05). Each twin had from zero to three clones producing IgG2 antibodies against type 1 Ps. A total of six different clones could be distinguished among all the twins. Vaccination enhanced the already actively secreting B-cell clones in 56 twins and newly recruited clones in 11 of the 84 twins; six among the 48 mono- and five among the 36 dizygotic twins. These new clones differed among the twins. Spectrotypes varied between all twins within the pairs. The fact that all twins differed in spectrotype is due to post-translational microheterogenity of the antibodies, events which are thus not genetically determined. The observation that even monozygotic twins possessed and responded with different clones within the pairs indicates that the V-region genes, which determine the final specificity of B cells, either differ from the original germ-line V region genes, e.g. owing to hypermutations or junctional diversity, or the rearranged germ-line genes occur accidentally although highly restricted.

Combinatorial Library Cloning of Human Antibodies toStreptococcus pneumoniaeCapsular Polysaccharides: Variable Region Primary Structures and Evidence for Somatic Mutation of Fab Fragments Specific for Capsular Serotypes 6B, 14, and 23F

“…First, only one or two distinct Fab fragments of any single serotype specificity were isolated from an individual donor, and in some cases these appeared to be intraclonal variants. This result is consistent with previous studies showing that Ab responses to PPS Ags are markedly oligoclonal and can be dominated by the products of a single clone (31,34,46). Second, the MNC populations used for library construction were enriched for specific B cells using PPS-coated paramagnetic beads and were obtained 7 days after vaccination, a time when there is an increased frequency of PPS-specific B cells in the peripheral circulation (38).…”

“…Although this interest stems primarily from the need to evaluate vaccine immunogenicity and to establish reliable surrogates of protection, the Ab response to PPS antigens (Ags) represents an ideal opportunity to examine the inheritance and development of protective immunity in humans. Ab responses to PPS Ags are markedly oligoclonal within individuals (31,34,46), and consequently variable (V) region diversity is limited. This property leads to individual variation in PPS-specific Ab fine specificity (41), avidity, and protective efficacy (52,66).…”

Placental Transfer of IgG and IgG Subclass Antibodies Anti‐Purified Escherichia coli LPS O16, O6 and O111

“…The clonotype can be considered as a 'fingerprint' of the antibody repertoire in an individual [23]. Slight modifications can be detected in this technique, such as post-translational modifications or even changes occurring after storage [23,24]. We can state that for various samples, or for most of them, the clonotypes found in the cord sera represented a mirror of the respective maternal sera (Figs 4 and 5).…”

Polysaccharide vaccines as probes of antibody repertoires in man

“…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),…”