Antigen selection in the IgE response of allergic and nonallergic individuals

Background: Affinity maturation within germinal centers should usually lead to an accumulation of replacement mutations in complementarity-determining regions (CDRs) of Ig genes as a result of antigen selection. A number of studies have suggested, but not statistically demonstrated, that antigen selection might not guide such an accumulation of replacement mutations in allergic IgE sequences. This has been suggested to reflect the nature of allergens themselves or of the allergic response. Objective: We sought to investigate the role of antigen selection in the evolution of the IgE response by mean of analysis of Ig sequences derived from both allergic and nonallergic individuals. Methods: IgE sequences were amplified from peripheral blood of allergic and nonallergic individuals by using seminested RTPCR. Additional IgE and IgG sequences were obtained from public databases. Analysis considered replacement mutations in the CDRs as a proportion of total mutations and compared IgE sequences with IgG sequences. Results: The nonallergic IgE sequences were significantly less mutated than both the allergic IgE (P < .001) and IgG (P < .01) sequences. There was a low proportion of replacement mutations in the CDRs of both nonallergic and allergic TgE sequences and a significantly increased proportion of such mutations in IgG sequences (P < .001). Conclusions: IgE antibodies in both nonallergic and allergic individuals appear to accumulate few somatic point mutations as a consequence of antigen selection. Clinical implications: Allergic and nonallergic IgE responses might often develop along a common pathway that is distinct from the conventional germinal center reaction through which the IgG response develops.