Molecular characteristics of anti-polysaccharide antibodies

Study of anti-carbohydrate antibodies in mice has been carried out with both environmental and bacterial polysaccharides. While the vast majority of polysaccharide antigens are T dependent and the antibodies are restricted to IgM and IgG3, polysaccharide coupled to a carrier, elicit T-dependent responses involving all Ig isotypes. Some polysaccharides can elicit immune responses after birth, other polysaccharides such as SIII, inulin and dextran, show a substantial ontogenic delay. Generally, anti-polysaccharide responses are oligoor pauciclonal. In the case of inulin, IEF analysis of antibodies showed only a few bands in all individuals, whereas in the case of levan, dextran or GAC the responses consists of a few spectrotypes shared by group of individual mice. The most striking characteristic of the IEF pattern of anti-polysaccharide antibodies is the small variation of spectrotypes during the time of the immune response, which generally is a long-lasting undulatory type of response. While the immune responses against protein antigens are encoded by V genes deriving from multiple VH and VL families, the most important characteristic of anti-polysaccharide responses is biased V gene family usage and restricted VH-Vχ pairing, which strikingly contrast with stoichiometric usage of V gene families and random VH-VL pairing in adult animals. Several comments can be made on the data summarized in Table 1: first, the utilization of a few V gene families in polysaccharide antibody response. Of particular interest is the over utilization of VHX4 which is composed only of two germ-line members. VHX24 genes were used in five different responses against galactan, β2-6 fructosan, fucosyl-galactosamine, Cryptococcus and N-acetyl glucosamine. It should be mentioned that the VH gene families composed of a few members are also predominantly used for antibodies specific for self haptens or other immunogenic components of bacterial cell wall. Thus, the majority of anti-phosphocholine antibodies are encoded by a single member (V1) of four members VHS107 family in association with Vχ22. Anti-BR-MRBC which recognize mainly the phosphatidylcholine are encoded by VH genes deriving from VH gene families composed only a few members namely VH10 and VH11. In these cases a strikingly restricted pairing was also noted, i.e. VH11-Vχ9, VH10-Vχ4. A second important feature consists in the lack of mutation in the coding region of VHX24 in anti-polysaccharide antibodies of various isotypes, as was observed in VH11 genes expressed in anti-BR-MRBC antibodies. This lack of genetic variation in VH genes indicates that both antigen-binding activity and idiotype expression (i.e., IdX) result from association with D segments and various light chains. While D segments exhibit a high degree of variability, the Vχ genes generally show little somatic mutation. Therefore, it is of considerable interest in the future to unravel the molecular mechanisms which govern restricted pairing of VHX24 with VL, and whether these VH gene families composed of only a few members have been conserved during the phylogeny. This would shed light on the possibility of conservation during the evolution of some VH gene families devoted to encoding responses against self and foreign environmental antigens.