Human regulatory B cells control the TFH cell response

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Presentation transcript:

Human regulatory B cells control the TFH cell response Achouak Achour, PhD, Quentin Simon, PhD, Audrey Mohr, MSc, Jean-François Séité, PhD, Pierre Youinou, MD, PhD, Boutahar Bendaoud, PharmD, Ibtissem Ghedira, PharmD, PhD, Jacques-Olivier Pers, DDS, PhD, Christophe Jamin, PhD  Journal of Allergy and Clinical Immunology  Volume 140, Issue 1, Pages 215-222 (July 2017) DOI: 10.1016/j.jaci.2016.09.042 Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Journal of Allergy and Clinical Immunology 2017 140, 215-222DOI: (10 Journal of Allergy and Clinical Immunology 2017 140, 215-222DOI: (10.1016/j.jaci.2016.09.042) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Breg cells inhibit TFH cell development but not differentiated T cells. A and B, Expression of TFH cell markers on CD4+ stimulated T cells cocultured with Breg cells (Fig 1, A) or nonstimulated B cells (Fig 1, B). C, Percentage of cells from purified CD4+ T cells. D, Expression of all markers on already differentiated TFH cells cocultured with Breg cells. *P < .05 and **P < .01 (Wilcoxon test). Results are means ± SEMs of 6 experiments. Journal of Allergy and Clinical Immunology 2017 140, 215-222DOI: (10.1016/j.jaci.2016.09.042) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Characterization of Breg cell–suppressive activity on TFH cell development. A, Expression and percentages at day 5 of TFH cell markers on stimulated T cells cocultured in a Transwell (TW) system. B and C, Time course (Fig 2, B) and percentages (Fig 2, C) with Breg cells or their supernatant (spt). D and E, Percentages after coculture with blocking antibodies. *P < .05, **P < .01, and ***P < .001 (Wilcoxon test). Results are means ± SEMs of 6 experiments. Journal of Allergy and Clinical Immunology 2017 140, 215-222DOI: (10.1016/j.jaci.2016.09.042) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Breg cells suppress TFH cell function. A, Frequencies of CD138+CD19+ plasma cells and CD19+IgD−CD27+ memory B cells during cocultures of B cells and TFH cells with Breg cells. B and C, Concentration of immunoglobulins in supernatants (Fig 3, B) and after cocultures with TFH cells from purified naive and memory T cells (Fig 3, C). TW, Transwell system. *P < .05, **P < .01, ***P < .001, and ****P < .0001 (Wilcoxon test). Results are means ± SEMs of 6 experiments. Journal of Allergy and Clinical Immunology 2017 140, 215-222DOI: (10.1016/j.jaci.2016.09.042) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 Characterization of Breg cell–suppressive effects on TFH cell function. A, IL-21R expression on T and B cells. B, Percentages of Foxp3+ T cells. C, Secretion of TGF-β and IL-10. D, Percentages of Foxp3+ T cells among CXCR5+PD-1+ T cells after coculture with blocking antibodies or in Transwell (TW) system. *P < .05, **P < .01, ***P < .001, and ****P < .0001 (Wilcoxon test). Results are means ± SEMs of 6 experiments. Journal of Allergy and Clinical Immunology 2017 140, 215-222DOI: (10.1016/j.jaci.2016.09.042) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 5 Breg cells suppress the function of in vivo–differentiated T cells. A, Concentration of immunoglobulins after cocultures of B cells with in vivo–differentiated CXCR5highPD-1high TFH cells or CXCR5−PD-1− T and Breg cells. B and C, Expression of TFH cell markers on sorted T cells after coculture. D, Percentages of Foxp3+ T cells among the sorted T cells after cocultures. *P < .05 and **P < .01 (Wilcoxon and Mann-Whitney tests). Results are means ± SEMs of 6 experiments. Journal of Allergy and Clinical Immunology 2017 140, 215-222DOI: (10.1016/j.jaci.2016.09.042) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions