Bursa of Fabricius (BF), one of primary lymphoid organ, is unique to birds. Meanwhile, lead (Pb) is well known for its high toxicology to birds. Therefore, this study aimed to examine the chronic toxic effects of lead exposure on BF in Japanese quails (C. japonica) and the underlying mechanism of lead immunotoxicity. One-week old male quails were exposed to 0 ppm, 50 ppm, 500 ppm and 1000 ppm Pb concentrations by drinking water for four weeks. The results showed that Pb accumulation in BF increased in a dose dependent way. The growth and development of BF was retarded in 500 ppm and 1000 ppm Pb groups. The number of lymphocytes was decreased and the release of immunoglobulin G and M (IgG, IgM), complement 3 and 4 (C3, C4) was inhibited by Pb exposure. Lead exposure also caused oxidative stress and increasing apoptosis in BF. Moreover, histopathological damages characterized by inflammatory hyperemia and inflammatory cell infiltration and ultrastructural injury featured by mitochondrial vacuole, cristae fracture and chromatin concentration were found in BF of 500 ppm and 1000 ppm Pb groups. Furthermore, RNA sequencing based transcriptomic analysis revealed that molecular signaling and functional pathways in BF were disrupted by lead exposure. In addition, the activation of Nuclear Factor kappa B (NF-κB) pathway while the inhibition of wingless integrated/catenin beta 1 (Wnt/β-catenin) signaling by Pb exposure were confirmed by quantitative real-time PCR (qPCR). Our study may benefit to understand potential mechanistic pathways of developmental immunotoxicology under Pb stress.

法氏囊 (BF) 是一种主要的淋巴器官，是鸟类独有的。同时，铅 (Pb) 因其对鸟类的高毒性而闻名。因此，本研究旨在探讨铅暴露对日本鹌鹑 ( C. japonica ) BF 的慢性毒性影响。) 以及铅免疫毒性的潜在机制。一周大的雄性鹌鹑通过饮用水暴露于 0 ppm、50 ppm、500 ppm 和 1000 ppm 浓度的铅 4 周。结果表明，BF中的Pb积累以剂量依赖性方式增加。BF 的生长和发展在 500 ppm 和 1000 ppm Pb 组中被延缓。淋巴细胞数量减少，免疫球蛋白 G 和 M（IgG、IgM）、补体 3 和 4（C3、C4）的释放受到铅暴露的抑制。铅暴露还导致 BF 中的氧化应激和细胞凋亡增加。此外，在500 ppm和1000 ppm Pb组的BF中发现了以炎性充血和炎性细胞浸润为特征的组织病理学损伤和以线粒体空泡、嵴断裂和染色质浓度为特征的超微结构损伤。此外，基于 RNA 测序的转录组分析显示，BF 中的分子信号传导和功能通路被铅暴露破坏。此外，通过定量实时 PCR (qPCR) 证实了 Pb 暴露激活了核因子 kappa B (NF-κB) 通路，同时抑制了无翼整合/连环蛋白β1 (Wnt/β-连环蛋白) 信号传导。我们的研究可能有助于了解铅胁迫下发育免疫毒理学的潜在机制途径。