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Institut National de la Santé et de la Recherche Médicale (INSERM), Unit 430 and Université Pierre et Marie Curie, Hôpital Broussais, Paris, France;
Research Institute of Hematology, Moscow, Russia;
Immunology Unit, Vall d’Hebron, Barcelona, Spain;
§
Department of Pediatrics, Soroka Medical Center, Beer Sheva, Israel;
¶
Department of Pediatrics, University of Brescia, Brescia, Italy;
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Institute of Immunology, University of Vienna, Vienna, Austria;
#
INSERM, Unit 429, Hôpital des Enfants-Malades, Paris, France; and
**
Department of Pediatrics, University of Washington Medical School, Seattle, WA 98195
We have analyzed the self-reactive repertoires of IgM and IgG Abs in the serum of 19 patients with hyper-IgM syndrome (HIM) by means of a quantitative immunoblotting technique that allows for a quantitative comparison of Ab repertoires in health and disease by multiparametric statistical analysis. Normal tissue extracts of liver, lung, stomach, and kidney were used as sources of self Ags. Extracts of Pseudomonas aeruginosa and Staphylococcus epidermidis were used as sources of nonself Ags. We demonstrate a significant bias in repertoires of reactivities of IgM of patients with HIM with self Ags. Ab repertoires of IgM toward nonself Ags did not differ, however, between patients and controls. No difference was found between IgM repertoires of untreated patients and those of patients receiving substitutive treatment 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 that was similar to that of IgG of healthy controls. The data demonstrate that functional CD40-CD40 ligand interactions are essential for the selection of natural self-reactive B cell repertoires.
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