Gaballa Joseph M, Valdez Caley, Mack Douglas G, Minhajuddin Faiz, Raza Masoom, Mohammad Tabrez A, Martin Allison K, Getahun Andrew, Dinarello Charles A, Fontenot Andrew P, Atif Shaikh M
Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.
Greehey Children's Cancer Research Institute, The University of Texas Health Science Center at San Antonio, San Antonio, TX, United States.
Front Immunol. 2025 Jan 28;16:1479348. doi: 10.3389/fimmu.2025.1479348. eCollection 2025.
Chronic beryllium disease (CBD) is a debilitating pulmonary disorder that occurs due to persistent exposure to beryllium (Be) particles in the workplace. Be-exposure causes activation of the innate immune system, resulting in the secretion of interleukins and chemokines that drive the accumulation of B and T cells in the lungs. However, the mechanisms by which innate molecules influence the recruitment of B cells and B cell-mediated protection in CBD are poorly understood. In this study, we employed multiple approaches to examine the role of innate immune signaling and CD4 T cells in B cell recruitment and function in the lungs. We show that the absence or blocking of IL-1R1 signaling prevents the recruitment of B cells to the lungs of BeO-exposed mice. Additionally, we show that B cell recruitment to the lungs depends on the chemokine receptor, CXCR5, and CD4 T cells. In BeO-exposed mice, lung B cells down-regulate IgM but showed an increased IgD and CD44 surface expression. Further, RNA sequencing of pulmonary tissue-specific B cells in CBD revealed distinct gene signatures compared to splenic B cells, with increased expression of pathways involved in antigen presentation, tight junction interactions, and interferon signaling. Overall, our study shows that B cell recruitment and aggregate formation during CBD depend on sequential activation of innate and adaptive immune responses.
慢性铍病（CBD）是一种使人衰弱的肺部疾病，它是由于在工作场所持续接触铍（Be）颗粒而发生的。接触铍会导致先天性免疫系统激活，从而导致白细胞介素和趋化因子的分泌，这些因子会促使B细胞和T细胞在肺部积聚。然而，先天性分子影响CBD中B细胞募集和B细胞介导的保护作用的机制尚不清楚。在本研究中，我们采用多种方法来研究先天性免疫信号传导和CD4 T细胞在肺部B细胞募集和功能中的作用。我们发现，IL-1R1信号传导的缺失或阻断可阻止B细胞募集到暴露于氧化铍（BeO）的小鼠肺部。此外，我们发现B细胞向肺部的募集依赖于趋化因子受体CXCR5和CD4 T细胞。在暴露于BeO的小鼠中，肺B细胞下调IgM，但显示IgD和CD44表面表达增加。此外，与脾B细胞相比，CBD中肺组织特异性B细胞的RNA测序揭示了不同的基因特征，参与抗原呈递、紧密连接相互作用和干扰素信号传导的通路表达增加。总体而言，我们的研究表明，CBD期间B细胞的募集和聚集形成依赖于先天性和适应性免疫反应的顺序激活。
