Laboratory of Dermatology and Immunodeficiencies, School of Medicine, University of São Paulo, LIM 56, São Paulo, Brazil.
BMC Immunol. 2010 Mar 11;11:11. doi: 10.1186/1471-2172-11-11.
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.
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.
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.
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。
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。
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。