顺序类转换从IgG1 B细胞产生抗原特异性肠道IgA，这一成果由耶鲁医学院Stephanie C. Eisenbarth研究团队经过不懈努力而取得。这一研究成果于2025年11月17日发表在国际顶尖学术期刊《免疫学》上。

事实上，课题组研究人员观察到通过生发中心（GC）和非GC途径产生亲和成熟的IgA B细胞。虽然大多数抗体同型是直接由幼稚的IgM B细胞产生的，但小组发现IgG1 GC B细胞可以在小鼠中产生肠黏膜IgA，在人类的粘膜和非粘膜部位也有类似的关系。这支持了一个通过顺序类转换产生IgA的模型，将粘膜IgA和全身IgG1体液免疫的特异性与肠道源性抗原联系起来。确定这些途径对于设计粘膜疫苗至关重要，因为需要产生IgA和IgG抗体来实现有效的屏障和系统保护。

据悉，免疫球蛋白（Ig）A是保护肠道屏障的主要同型，但抗原特异性IgA诱导的基本方面仍不清楚。肠道淋巴器官长期暴露于外来抗原，在结构上不同于其他淋巴组织，在功能上也是独一无二的。这表明肠道IgA诱导是通过非规范方式发生的。

附：英文原文

Title: Sequential class switching generates antigen-specific gut IgA from IgG1 B cells

Author: Emily R. Siniscalco, Hailong Meng, Gisela Gabernet, Gaspar. A. Pacheco, Shahab Saghaei, Sydney I. Ramirez, L. Benjamin Hills, Farhoud Faraji, Shuting Chen, Xiangyun Yin, Christine Dien, Laura R. Hoyt, Elise G. Liu, Abel Barrett, Neima Briggs, Adam Williams, Vipul Shukla, Shane Crotty, Duane R. Wesemann, Steven H. Kleinstein, Joe Craft, Stephanie C. Eisenbarth

Issue&Volume: 2025-11-17

Abstract: Immunoglobulin (Ig)A is the primary isotype protecting the gut barrier, yet fundamental aspects of antigen-specific IgA induction remain unknown. Gut lymphoid organs are chronically exposed to foreign antigens, are structurally different from other lymphoid tissues, and are functionally unique. This suggests gut IgA induction occurs through noncanonical means. Indeed, we observed the generation of affinity-matured IgA B cells through both germinal center (GC) and nonGC pathways. Although most antibody isotypes are generated directly from naive IgM B cells, we discovered that IgG1 GC B cells can generate gut mucosal IgA in mice, with a similar relationship in mucosal and non-mucosal sites in humans. This supports a model of IgA generation through sequential class switching, linking the specificity of mucosal IgA and systemic IgG1 humoral immunity to gut-derived antigens. Defining these pathways is essential for the design of mucosal vaccines, which need to generate IgA and IgG antibodies for efficient barrier and systemic protection.

DOI: 10.1016/j.immuni.2025.10.022

Source: https://www.cell.com/immunity/abstract/S1074-7613(25)00476-5