Mikami Yoshikazu, Hayatsu Manabu, Kuroda Etsushi, Tsuda Hiromasa, Toriumi Taku, Mizutani Yusuke, Ichinose Takamichi, Honda Akiko, Takano Hirohisa
Division of Microscopic Anatomy, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
Department of Immunology, Hyogo College of Medicine, Nishinomiya, Japan.
Front Immunol. 2025 Aug 4;16:1578255. doi: 10.3389/fimmu.2025.1578255. eCollection 2025.
Inducible bronchus-associated lymphoid tissue (iBALT) develops with different morphologies and functions depending on the type of antigen, in which various cytokines, such as interleukin (IL)-1 and IL-17, and the cells producing them, such as T helper 17 (Th17) and T follicular helper (T) cells, play an important role. We recently observed that numerous inflammatory cells, mainly B cell like-cells forming peribronchial clusters, accumulate in the lungs of mice exposed to Asian sand dust (ASD), suggesting that ASD induced iBALT development. However, whether ASD induced iBALT formation, much less the mechanism by which ASD promotes iBALT formation, remains unknown.
B cell clusters were analyzed using the next generation serial section-three-dimensional (nSS3D) imaging method, in which we attempted to introduce batch image acquisition using a high-resolution slide scanner and AI-based image registration and target extraction. Furthermore, the mechanism underlying ASD-induced B-cell cluster formation was examined using CD4-Cre Bcl6 mice lacking T cells.
ASD induced B-cell cluster formation in mouse lung tissue, which was enhanced by allergen (Ovalbumin: OVA) exposure. Furthermore, the nSS3D images revealed that a part of the B cell clusters induced by OVA+ASD but not others exhibited common histological features of previously reported iBALTs. Moreover, OVA+ASD exposure failed to induce all of the B cell cluster formation including iBALTs in CD4-Cre Bcl6 mice.
B cell clusters including iBALTs are induced by ASD; this process is enhanced by OVA, in which T cells were suggested to play important roles. Characterization of the OVA+ASD-induced B cell clusters proved that the SS3D technique is useful for the analysis of mouse disease models. The results also emphasize the need for medical countermeasures for patients with allergic diseases living in areas with ASD contamination.
诱导性支气管相关淋巴组织（iBALT）根据抗原类型的不同而呈现出不同的形态和功能，其中多种细胞因子，如白细胞介素（IL）-1和IL-17，以及产生这些细胞因子的细胞，如辅助性T细胞17（Th17）和滤泡辅助性T（Tfh）细胞，发挥着重要作用。我们最近观察到，在暴露于亚洲沙尘（ASD）的小鼠肺部，大量炎症细胞（主要是形成支气管周围簇的B细胞样细胞）聚集，提示ASD诱导了iBALT的发育。然而，ASD是否诱导了iBALT的形成，更不用说ASD促进iBALT形成的机制，仍然未知。
使用下一代连续切片三维（nSS3D）成像方法分析B细胞簇，我们尝试使用高分辨率载玻片扫描仪引入批量图像采集以及基于人工智能的图像配准和目标提取。此外，使用缺乏T细胞的CD4-Cre Bcl6小鼠研究ASD诱导B细胞簇形成的潜在机制。
ASD诱导小鼠肺组织中B细胞簇的形成，过敏原（卵清蛋白：OVA）暴露可增强这一过程。此外，nSS3D图像显示，OVA+ASD诱导的部分B细胞簇（而非其他B细胞簇）表现出先前报道的iBALT的共同组织学特征。此外，OVA+ASD暴露未能在CD4-Cre Bcl6小鼠中诱导包括iBALT在内的所有B细胞簇的形成。
包括iBALT在内的B细胞簇由ASD诱导形成；OVA可增强这一过程，提示T细胞在其中发挥重要作用。对OVA+ASD诱导的B细胞簇的表征证明，SS3D技术可用于分析小鼠疾病模型。研究结果还强调了为生活在ASD污染地区的过敏性疾病患者采取医疗对策的必要性。
