Isotype restriction of idiotopes associated with human anti-streptococcal A carbohydrate antibodies

Sharing of idiotopes between IgG and IgM antibodies has been described with antibodies of various specificities in the literature. However, this does not seem to be the rule for human IgG and IgM antibodies with specificity to streptococcal A carbohydrate. Six idiotopes were described which are associated either with IgM or with IgG antibodies to one of the two major epitopes of streptococcal A carbohydrate: N-acetyl-D-glucosamine or alpha(1,2), alpha(1,3)-linked rhamnose oligomers. Some of the idiotopes are widely cross-reactive with antibodies of the corresponding specificity in other individuals. They were constantly found to be restricted to either IgM or IgG in all individuals tested so far. We discuss several alternatives to explain this finding and conclude that switching from IgM to IgG is either a very rare event in human B cells of this specificity, or leads to loss and gain of idiotopes and/or specificity due to frequent somatic mutations. The phenomenon of idiotope restriction to certain isotypes might be important if anti-idiotopic monoclonal antibodies are considered for use in therapeutical approaches aimed at the manipulation of antibody production.