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

Sébastien Lacroix-Desmazes, Igor Resnick, Dorothea Stahl, Luc Mouthon, Teresa Espanol, Jacov Levy, Srini V. Kaveri, Luigi Notarangelo, Martha Eibl, Alain Fischer, Hans Ochs, Michel D. Kazatchkine

    Research output: Contribution to journalArticlepeer-review

    35 Scopus citations

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)5601-5608
    Number of pages8
    JournalJournal of Immunology
    Volume162
    Issue number9
    StatePublished - 1 May 1999

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology

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