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Human newborn B cells mount an interferon-α/β receptor-dependent humoral response to respiratory syncytial virus  Jop Jans, MD, Matthew Pettengill, PhD,

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Presentation on theme: "Human newborn B cells mount an interferon-α/β receptor-dependent humoral response to respiratory syncytial virus  Jop Jans, MD, Matthew Pettengill, PhD,"— Presentation transcript:

1 Human newborn B cells mount an interferon-α/β receptor-dependent humoral response to respiratory syncytial virus  Jop Jans, MD, Matthew Pettengill, PhD, Dhohyung Kim, PhD, Cas van der Made, BSc, Ronald de Groot, MD, PhD, Stefanie Henriet, MD, PhD, Marien I. de Jonge, PhD, Gerben Ferwerda, MD, PhD, Ofer Levy, MD, PhD  Journal of Allergy and Clinical Immunology  Volume 139, Issue 6, Pages e4 (June 2017) DOI: /j.jaci Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 Fig 1 A-H, RSV induces IFNAR-dependent activation of newborn B cells. CD69+ B cells after 18-hour stimulation of (Fig 1, A) MCs or (Fig 1, B-C) newborn B cells (N = 5-11). Induction of (Fig 1, D) IFN-α and (Fig 1, E) IFN-β in MCs. CD69+ B cells after 18-hour stimulation of (Fig 1, F and G) newborn B cells or (Fig 1, H) adult B cells in the absence or presence of anti–IFNAR-blocking antibodies or isotype controls (N = 3-5) (mean ± SEM). INFAR, Interferon-α/β receptor; NS, not significant. *P < .05. **P < .01. ***P < .001. Journal of Allergy and Clinical Immunology  , e4DOI: ( /j.jaci ) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 Fig 2 A-F, RSV-IgM ASCs in newborns and functional RSV-IgM in neonatal plasma that reduces RSV infection. (Fig 2, A) Total-IgM ASC or (Fig 2, B) RSV-IgM ASCs determined by Enzyme-linked Immunospot. N = 5-8. Fig 2, C, RSV-IgM plasma concentrations. N = 6-9. (Fig 2, D) Microscope images and (Fig 2, E) quantification of fluorescent A549 cells after exposure to RSV in medium, purified newborn IgM (RSV + IgM), or newborn plasma (RSV + plasma). N = 3. (mean ± SEM). Fig 2, F, Graphical summary of the IFNAR-dependent humoral response to RSV in newborns. INFAR, Interferon-α/β receptor; NS, not significant. *P < .05. **P < .01. ***P < .001. ϕϕϕNewborn vs adult: P < .001. Journal of Allergy and Clinical Immunology  , e4DOI: ( /j.jaci ) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4 Fig E1 A-D, Soluble mediators activate adult isolated B cells. Representative gating strategy to determine (Fig E1, A) CD69+ B cells or (Fig E1, B) CD86+ cells. Fig E1, C, Percentage of CD86+ B cells after stimulation of newborn isolated B cells (N = 5). Fig E1, D, Percentage of CD69+ B cells after stimulation of adult isolated B cells with IFN-α or IFN-β (N = 5) (mean ± SEM). 7-AAD, 7-Aminoactinomycin D; FSC, forward-scattered light; SSC, side-scattered light. *P < .05. ***P < .001. Journal of Allergy and Clinical Immunology  , e4DOI: ( /j.jaci ) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5 Fig E2 A-D, IFNAR-dependent activation of newborn and adult B cells after exposure to IFN-β. Fig E2, A, Percentage of CD69+ B cells (N = 6). Fig E2, B, Expression of IFNAR1 and IFNAR2 on newborn and adult B cells (N = 5-6). Percentage of CD69+ B cells after stimulation of (Fig E2, C) newborn or (Fig E2, D) adult MCs with IFN-β (500 IU/mL) in the absence or presence of anti–IFNAR-blocking antibodies or isotype controls (N = 5) (mean ± SEM). INFAR, Interferon-α/β receptor; NS, not significant. *P < .05. **P < .01. ***P < .001. Journal of Allergy and Clinical Immunology  , e4DOI: ( /j.jaci ) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

6 Fig E3 A-C, Purified IgM reduces RSV infection of epithelial cells. Fig E3, A, Representative ELISpot of total-IgM, RSV-IgM, and total-IgG ASCs. Fig E3, B, Total-IgG ASC (ASC/1 × 106 plated cells) after stimulation of MCs with RSV (MOI, 0.5) (N = 5-9). Fig E3, C, Percentage of RSV-infected GFP+ A549 cells after exposure to RSV (MOI, 2.5) in medium or to RSV in medium with purified newborn IgM from 4 different donors (mean ± SEM). GFP, Green fluorescent protein; MOI, multiplicity of infection; NS, not significant. *P < .05. **P < .01. ϕϕNewborn vs adult: P < .01. Journal of Allergy and Clinical Immunology  , e4DOI: ( /j.jaci ) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

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