IgE-class–specific immunosuppression in offspring by administration of anti-IgE to pregnant mice Hideaki Morita, MD, PhD, Masato Tamari, MD, PhD, Masako.

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Presentation transcript:

IgE-class–specific immunosuppression in offspring by administration of anti-IgE to pregnant mice Hideaki Morita, MD, PhD, Masato Tamari, MD, PhD, Masako Fujiwara, BSc, Kenichiro Motomura, MD, PhD, Yasuhiko Koezuka, PhD, Go Ichien, PhD, Kenji Matsumoto, MD, PhD, Kimishige Ishizaka, MD, PhD, Hirohisa Saito, MD, PhD Journal of Allergy and Clinical Immunology Volume 143, Issue 3, Pages 1261-1264.e6 (March 2019) DOI: 10.1016/j.jaci.2018.11.008 Copyright © 2018 The Authors Terms and Conditions

Fig 1 Experimental protocols. Pregnant mice were intravenously (i.v.) injected with anti–IgE antibody or isotype antibody on embryonic 12.5 days (E12.5) and E18.5. Offspring were intraperitoneally (i.p.) injected with OVA or saline emulsified with alum, twice at an interval of 1 week (ie, on PND2 and PND9 for protocol A, PND16 and PND23 for protocol B, PND30 and PND37 for protocol C, and PND44 and PND51 for protocol D). Sera were collected 14 days after the second injection. Journal of Allergy and Clinical Immunology 2019 143, 1261-1264.e6DOI: (10.1016/j.jaci.2018.11.008) Copyright © 2018 The Authors Terms and Conditions

Fig 2 Production of antigen-specific IgE and IgG1 antibodies by offspring that had been injected with anti-IgE during the fetal period. C57BL/6 mice (A and B) (n = 5-16 per group) or BALB/c mice (C and D, shown in dark red) (n = 3-19 per group) were used. The serum levels of OVA-specific IgE antibody (Fig 2, A and C) and OVA-specific IgG1 antibody (Fig 2, B and D) are shown for each protocol (see legend for Fig 1). N.S., Nonsignificant; Sal, saline. N.S. for P ≥ .05, *P < .05, **P < .01, and ***P < .001. Journal of Allergy and Clinical Immunology 2019 143, 1261-1264.e6DOI: (10.1016/j.jaci.2018.11.008) Copyright © 2018 The Authors Terms and Conditions

Fig E1 Antigen-specific cytokine production by spleen cells from the offspring. Spleen cells were obtained from C57BL/6 mice (A) or BALB/c mice (B, shown in dark red) at the same time as blood sampling according to each protocol shown in the legend to Fig 1. The cells were cultured with OVA or medium alone for 72 hours. ELISA was performed to determine the levels of cytokines in the culture supernatants. Data show the mean ± SEM (n = 5-10). *P < .05, **P < .01, and ***P < .001 vs the corresponding value for the culture with medium alone. N.S., No significant difference (P ≥ .05) between the indicated groups. Journal of Allergy and Clinical Immunology 2019 143, 1261-1264.e6DOI: (10.1016/j.jaci.2018.11.008) Copyright © 2018 The Authors Terms and Conditions

Fig E1 Antigen-specific cytokine production by spleen cells from the offspring. Spleen cells were obtained from C57BL/6 mice (A) or BALB/c mice (B, shown in dark red) at the same time as blood sampling according to each protocol shown in the legend to Fig 1. The cells were cultured with OVA or medium alone for 72 hours. ELISA was performed to determine the levels of cytokines in the culture supernatants. Data show the mean ± SEM (n = 5-10). *P < .05, **P < .01, and ***P < .001 vs the corresponding value for the culture with medium alone. N.S., No significant difference (P ≥ .05) between the indicated groups. Journal of Allergy and Clinical Immunology 2019 143, 1261-1264.e6DOI: (10.1016/j.jaci.2018.11.008) Copyright © 2018 The Authors Terms and Conditions

Fig E2 The changes in body temperature of mice after intraperitoneal challenge with OVA in C57BL/6 mice (A) and BALB/c mice (B, shown in dark red) (n = 8-18 per group). Data represent the mean ± SEM. *P < .05. We did not perform further experiments using BALB/c mice in protocols C and D, because we realized that IgG1-dependent anaphylaxis might occur when the level of anti-OVA IgG1 was increased, and that this phenomenon would occur in mice but not in humans. Journal of Allergy and Clinical Immunology 2019 143, 1261-1264.e6DOI: (10.1016/j.jaci.2018.11.008) Copyright © 2018 The Authors Terms and Conditions

Fig E3 Total IgE in the sera from naive mice in BALB/c (A) and BALB/c mice (B, shown in dark red). Total IgE in each serum was determined by ELISA. n = 4-6 per group. The mean ± SEM are shown. *P < .05. Journal of Allergy and Clinical Immunology 2019 143, 1261-1264.e6DOI: (10.1016/j.jaci.2018.11.008) Copyright © 2018 The Authors Terms and Conditions

Fig E4 One possible explanation as to why anti-IgE blocks IgE production during perinatal period but not afterwards. A, When anti-IgE is present in mice almost lacking IgE, that is, like a fetus, it may induce apoptosis of mIgE+ B cells by binding to the membrane proximal domain of the receptor. B, In the presence of antigen, IL-4, and CD40L, mIgE+ B cells can produce IgE. C, When anti-IgE is present in mice having considerable levels of IgE, binding of anti-IgE to mIgE may be blocked by excessive IgE. Meanwhile, anti-IgE acts on effector cells by blocking binding of IgE to Fc ε receptors. Journal of Allergy and Clinical Immunology 2019 143, 1261-1264.e6DOI: (10.1016/j.jaci.2018.11.008) Copyright © 2018 The Authors Terms and Conditions