The Role of Basophils in Adaptive Immunity

描述(由申请人提供)：免疫球蛋白介导的过敏性疾病，包括过敏性鼻结膜炎和食物过敏，患病率正在上升，1-4尽管控制IgE反应持久性的机制仍未确定。嗜碱性粒细胞可在变应原刺激下，通过表面IgE的交联化释放炎症介质，从而介导变态反应效应。它们还被推测在小鼠模型的体液反应中发挥作用，并被证明能诱导B细胞产生IgE。我们假设人类嗜碱性粒细胞可以诱导人B细胞的IgE以一种依赖于IgE和激活的方式传播过敏反应。关于持续性IgE产生的起源，争论的焦点是：IgE是由发源于生发中心的IgE记忆B细胞产生的，还是由产生免疫球蛋白的记忆B细胞产生的顺序的IgE类转换的结果。嗜碱性粒细胞已经被证明可以运输到淋巴结，我们假设嗜碱性粒细胞可以通过诱导有序的类别转换有效地诱导记忆B细胞产生IgE。我们进一步推测，嗜碱性粒细胞以IgE介导的方式内吞过敏原的能力也可能允许它们向B细胞递送过敏原，以传播过敏原特异性反应。

DESCRIPTION (provided by applicant): IgE-mediated allergic diseases, including allergic rhinoconjunctivitis and food allergies, are rising in prevalence,1-4 though the mechanisms that govern the persistence of IgE responses continue to remain unidentified. Basophils can mediate allergic effector responses by releasing inflammatory mediators on cross-linking of surface IgE on allergen stimulation. They have also been speculated to play a role in humoral responses in murine models and have been shown to induce IgE production from B cells. We hypothesize that human basophils can induce IgE from human B cells to propagate the allergic response in an IgE and activation dependent manner. Controversy on the origin of persistent IgE production centers on whether IgE is produced by IgE memory B cells originating from germinal centers or results from sequential IgE class switching from IgG producing memory B cells. Basophils have been shown to traffic to lymph nodes, and we hypothesize that basophils can induce IgE production from memory B cells by induction of sequential class switching efficiently. We further speculate that the ability of basophils to endocytose allergen in an IgE mediated fashion may also allow them to present allergens to B cells to propagate an allergen-specific response.