Defective self-reactive antibody repertoire of serum IgM in patients with hyper-IgM syndrome

We have analyzed the self-reactive repertoires of IgM and IgG Abs in the se rum of 19 patients with hyper-IgM syndrome (HIM) by means of a quantitative immunoblotting technique that allows for a quantitative comparison of Ab r epertoires in health and disease by multiparametric statistical analysis. N ormal tissue extracts of liver, lung, stomach, and kidney were used as sour ces of self Ags. Extracts of Pseudomonas aeruginosa and Staphylococcus epid ermidis were used as sources of nonself Ags, We demonstrate a significant b ias in repertoires of reactivities of IgM of patients with HIM with self Ag s. Ab repertoires of IgM;I toward nonself Ags did not differ, however, betw een patients and controls. No difference was found between IgA I repertoire s of untreated patients and those of patients receiving substitutive treatm ent with i.v, IgG. IgG in the serum of HIM patients lacked reactivity with self Ags, although it exhibited a pattern of reactivity with nonself Ags th at was similar to that of IgG of healthy controls. The data demonstrate tha t functional CD40-CD40 ligand interactions are essential for the selection of natural self-reactive B cell repertoires.