Interleukin-1 Signaling and CD4+ T Cells Control B Cell Recruitment to the Lungs in Chronic Beryllium Disease

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-1 receptor 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. Further, RNA sequencing of pulmonary tissue-resident 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 are dependent on sequential activation of both innate and adaptive immune responses. RNA sequencing of beads and FACS sorted B cells from the lungs of BeO-exposed mice and CD23+ follicular B cells from the spleens of PBS-treated mice. The transcriptional changes were compared between the lung B cells and splenic follicular B cells.