Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY.
Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY
J Immunol. 2022 Aug 15;209(4):665-674. doi: 10.4049/jimmunol.2101081. Epub 2022 Jul 27.
Production and secretion of IgE by B cells, plasmablasts, and plasma cells is a central step in the development and maintenance of allergic diseases. IgE can bind to one of its receptors, the low-affinity IgE receptor CD23, which is expressed on activated B cells. As a result, most B cells bind IgE through CD23 on their surface. This makes the identification of IgE producing cells challenging. In this study, we report an approach to clearly identify live IgE plasmablasts in peripheral blood for application by both flow cytometry analysis and in vitro assay. These IgE plasmablasts readily secrete IgE, upregulate specific mRNA transcripts (BLIMP-1 IRF4, XBP1, CD138, and TACI), and exhibit highly differentiated morphology all consistent with plasmablast differentiation. Most notably, we compared the presence of IgE plasmablasts in peripheral blood of allergic and healthy individuals using a horse model of naturally occurring seasonal allergy, hypersensitivity. The model allows the comparison of immune cells both during periods of clinical allergy and when in remission and clinically healthy. Allergic horses had significantly higher percentages of IgE plasmablasts and IgE secretion while experiencing clinical allergy compared with healthy horses. Allergy severity and IgE secretion were both positively correlated to the frequency of IgE plasmablasts in peripheral blood. These results provide strong evidence for the identification and quantification of peripheral IgE-secreting plasmablasts and provide a missing cellular link in the mechanism of IgE secretion and upregulation during allergy.
B 细胞、浆母细胞和浆细胞产生和分泌 IgE 是过敏性疾病发生和维持的核心步骤。IgE 可以与其中一个受体，即低亲和力 IgE 受体 CD23 结合，而 CD23 表达于活化的 B 细胞上。因此，大多数 B 细胞通过其表面的 CD23 结合 IgE。这使得鉴定 IgE 产生细胞具有挑战性。在这项研究中，我们报告了一种方法，可以清楚地鉴定外周血中的活 IgE 浆母细胞，用于流式细胞分析和体外测定。这些 IgE 浆母细胞容易分泌 IgE，上调特异性 mRNA 转录本（BLIMP-1、IRF4、XBP1、CD138 和 TACI），并表现出高度分化的形态，所有这些都与浆母细胞分化一致。值得注意的是，我们使用自然发生的季节性过敏（超敏反应）马模型比较了过敏和健康个体外周血中 IgE 浆母细胞的存在。该模型允许在临床过敏和缓解期以及临床健康时比较免疫细胞。与健康马相比，患有过敏的马在经历临床过敏时，IgE 浆母细胞和 IgE 分泌的百分比明显更高。过敏严重程度和 IgE 分泌均与外周血中 IgE 浆母细胞的频率呈正相关。这些结果为鉴定和定量外周 IgE 分泌浆母细胞提供了有力证据，并为过敏期间 IgE 分泌和上调的机制提供了缺失的细胞联系。
