A8.27 Control of the humoral response by regulatory B cells.

Abstract : BACKGROUND AND OBJECTIVES: Follicular helper T (Tfh) cells are instrumental in the development of humoral responses. They support the terminal differentiation of B cells into memory and antibody-producing cells within germinal centers. Regulatory B (Breg) cells can modulate inflammatory reactions through the control of dendritic cell maturation and function, and through the control of T cell proliferation and Th1 polarization. Our aimed was to evaluate the control of humoral responses by Breg cells. MATERIALS AND METHODS: We developed in vitro models of human Tfh cell polarisation and function. They were obtained by stimulation of purified T cells with anti-CD3 and anti-CD28 Abs in the presence of IL-12 and IL-21. Expression of Bcl-6, IL-21, ICOS, CXCR5 and PD-1, all characteristics of Tfh cells were determined by flow cytometry. Tfh functions were studied by co-cultures with non-stimulated purified B cells. Their differentiation into memory and plasma cells was appraised by flow cytometry and by ELISA to measure the production of immunolgobulins. Breg cells were obtained by stimulation of purified B cells with CpG-ODN on CD40L-transfected fibroblasts. Their effect on Tfh cell maturation and function were studied in co-culture experiments. RESULTS: in vitro Tfh cells were obtained. Thus, Bcl-6 was up-regulated, IL-21 induced and ICOS, CXCR5 and PD-1 expression increased after stimulation. Furthermore, differentiated Tfh cells fostered the maturation of IgD-CD27 + memory B cells and CD138 + plasma cells, and triggered the secretion of IgM, IgG and IgA. Added to the T cells, Breg cells restrained the expression of Tfh markers. In the co-cultures of Tfh with B cells, Breg cells inhibited the induction of IgD-CD27 + and CD138 + B cells. They also impeded the secretion of immunoglobulins. Using blocking antibodies, suppressive activities of Bregs were found to be dependent on IL-10 and TGFbeta and based on direct contact with Tfh cells involving CD40, CD80, CD86 and CD54 molecules. CONCLUSIONS: Human Breg cells can modulate the development of humoral responses through the control of Tfh cell polarization and of Tfh-dependent terminal differentiation of B cells. Whether these properties are impaired and responsible for abnormal humoral responses in autoimmune diseases needs now to be established.
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Article dans une revue
Annals of the Rheumatic Diseases, BMJ Publishing Group, 2014, 73 Suppl 1, pp.A86-8. 〈10.1136/annrheumdis-2013-205124.201〉
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Contributeur : Geneviève Michel <>
Soumis le : jeudi 20 février 2014 - 16:06:58
Dernière modification le : mercredi 29 novembre 2017 - 14:53:50

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Christophe Jamin, Achouak Achour, Pierre Youinou, Jacques-Olivier Pers. A8.27 Control of the humoral response by regulatory B cells.. Annals of the Rheumatic Diseases, BMJ Publishing Group, 2014, 73 Suppl 1, pp.A86-8. 〈10.1136/annrheumdis-2013-205124.201〉. 〈hal-00950053〉

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