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母源性卵清蛋白免疫接种可预防新生儿过敏的发生,并上调 B 细胞上抑制性受体 FcγRIIB 的表达。

Maternal immunization with ovalbumin prevents neonatal allergy development and up-regulates inhibitory receptor Fc gamma RIIB expression on B cells.

机构信息

Laboratory of Dermatology and Immunodeficiencies, School of Medicine, University of São Paulo, LIM 56, São Paulo, Brazil.

出版信息

BMC Immunol. 2010 Mar 11;11:11. doi: 10.1186/1471-2172-11-11.

Abstract

BACKGROUND

Preconception allergen immunization prevents neonatal allergen sensitization in mice by a complex interaction between regulatory cells/factors and antibodies. The present study assessed the influence of maternal immunization with ovalbumin (OVA) on the immune response of 3 day-old and 3 week-old offspring immunized or non-immunized with OVA and evaluated the effect of IgG treatment during fetal development or neonatal period.

RESULTS

Maternal immunization with OVA showed increased levels of Fc gamma RIIb expression in splenic B cells of neonates, which were maintained for up to 3 weeks and not affected by additional postnatal OVA immunization. Maternal immunization also exerted a down-modulatory effect on both IL-4 and IFN-gamma-secreting T cells and IL-4 and IL-12- secreting B cells. Furthermore, immunized neonates from immunized mothers showed a marked inhibition of antigen-specific IgE Ab production and lowered Th2/Th1 cytokine levels, whereas displaying enhanced Fc gamma RIIb expression on B cells. These offspring also showed reduced antigen-specific proliferative response and lowered B cell responsiveness. Moreover, in vitro evaluation revealed an impairment of B cell activation upon engagement of B cell antigen receptor by IgG from OVA-immunized mice. Finally, in vivo IgG transference during pregnancy or breastfeeding revealed that maternal Ab transference was able to increase regulatory cytokines, such as IL-10, in the prenatal stage; yet only the postnatal treatment prevented neonatal sensitization. None of the IgG treatments induced immunological changes in the offspring, as it was observed for those from OVA-immunized mothers.

CONCLUSION

Maternal immunization upregulates the inhibitory Fc gamma RIIb expression on offspring B cells, avoiding skewed Th2 response and development of allergy. These findings contribute to the advancement of prophylactic strategies to prevent allergic diseases in early life.

摘要

背景

变应原免疫预防通过调节细胞/因子和抗体的复杂相互作用来预防新生鼠的变应原致敏。本研究评估了卵清蛋白(OVA)致敏的母体对 3 日龄和 3 周龄后代用 OVA 进行免疫或非免疫的免疫反应的影响,并评估了在胎儿发育或新生儿期进行 IgG 治疗的效果。

结果

OVA 致敏的母体显示出新生鼠脾 B 细胞中 FcγRIIb 表达水平增加,这种增加可持续至 3 周,并且不受随后的新生鼠 OVA 免疫的影响。母体免疫还对产生 IL-4 和 IFN-γ的 T 细胞以及产生 IL-4 和 IL-12 的 B 细胞产生下调作用。此外,来自致敏母亲的免疫新生鼠显示出抗原特异性 IgE Ab 产生的显著抑制和 Th2/Th1 细胞因子水平降低,而 B 细胞上的 FcγRIIb 表达增强。这些后代还显示出抗原特异性增殖反应降低和 B 细胞反应性降低。此外,体外评估显示,OVA 免疫的小鼠的 IgG 与 B 细胞抗原受体结合后,B 细胞的激活受到损害。最后,在怀孕期间或哺乳期进行体内 IgG 转移发现,母体 Ab 转移能够在产前阶段增加调节性细胞因子,如 IL-10;然而,只有产后治疗才能预防新生鼠致敏。与来自 OVA 免疫的母亲的后代一样,没有观察到 IgG 治疗在后代中引起免疫变化。

结论

母体免疫上调了后代 B 细胞上的抑制性 FcγRIIb 表达,避免了偏向性 Th2 反应和过敏的发展。这些发现有助于推进预防生命早期过敏疾病的预防性策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5392/2848204/1ad21bf77922/1471-2172-11-11-1.jpg

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