Intravenous immunoglobulin induces a functional silencing program similar to anergy in human B cells.

Abstract : BACKGROUND: Chronic inflammatory and autoimmune diseases are largely due to inappropriate response of hyperactive or autoreactive B cells. These autoreactive B cells can evade central tolerance checkpoints and migrate to the periphery, where they would be silenced by anergy. Such anergic cells are characterized by B-cell receptor (BCR) desensitization and altered downstream signaling. OBJECTIVE: We sought to determine whether intravenous immunoglobulin (IVIg) induces a nonresponsive state of B cells and to address the similarities of this mechanism to those described in anergy. METHODS: Human B cells were stimulated with anti-IgM antibody, and effects of IVIg on several parameters, such as calcium release, tyrosine phosphorylation, BCR aggregation, BCR internalization, or transcriptional activity, were studied by using flow cytometry, confocal microscopy, Western blotting, and a quantitative PCR array. RESULTS: IVIg-treated B cells show defects in activating coreceptor expression, calcium signaling, and BCR aggregation on engagement by antigen. IVIg also induces suppression of phosphoinositide 3-kinase signaling, which plays a central role in determining B-cell fate. All these events ultimately lead to profound modifications in gene expression, resulting in long-term functional but reversible silencing of IVIg-treated B cells. CONCLUSION: Our findings provide insights into the effectiveness of IVIg in treating autoimmune or inflammatory pathologies associated with the loss of B-cell tolerance. Furthermore, these data provide a model to explore the complexity of positive versus negative selection in B cells.
Type de document :
Article dans une revue
Journal of Allergy and Clinical Immunology, Elsevier, 2014, 133 (1), pp.181-188.e9. 〈10.1016/j.jaci.2013.08.042〉
Liste complète des métadonnées

http://hal.univ-brest.fr/hal-00926676
Contributeur : Geneviève Michel <>
Soumis le : vendredi 10 janvier 2014 - 09:20:45
Dernière modification le : mercredi 29 novembre 2017 - 14:53:50

Identifiants

Collections

Citation

Jean-François Séïté, Carole Goutsmedt, Pierre Youinou, Jacques-Olivier Pers, Sophie Hillion. Intravenous immunoglobulin induces a functional silencing program similar to anergy in human B cells.. Journal of Allergy and Clinical Immunology, Elsevier, 2014, 133 (1), pp.181-188.e9. 〈10.1016/j.jaci.2013.08.042〉. 〈hal-00926676〉

Partager

Métriques

Consultations de la notice

83