Changes in the thymus and potential mechanisms underlying the pathogenesis in pristane-induced lupus (PIL) mice are poorly understood. This study aimed to systematically and specifically examine changes in the thymus and the potential mechanisms responsible for immunological abnormalities in PIL mice. The results showed that PIL mice exhibit serious thymic hyperplasia, an elevated thymus index, a damaged histopathological structure and increased thymocyte apoptosis. We found that thymic T cell differentiation was impaired as the CD4⁺ CD8⁺ double-positive (DP) thymocyte frequency significantly decreased, becoming almost absent at 28 weeks after induction, while CD4 CD8^- double-negative (DN) thymocytes and CD4⁺ CD8^- single-positive (CD4⁺ SP) and CD4 CD8⁺ single-positive (CD8⁺ SP) cells were increased. This phenomenon might be explained by an inhibition of the DN-to-DP-cell transition and stimulation of DP cell conversion into CD4⁺ /CD8⁺ SP thymocytes. Moreover, we discovered a dramatic and abnormal increase in thymic B cells, that was associated with CD19, Irf8, Ebf1, Pax5, Irf4, Blk, CXCL13, CXCR5, CD79a, CD79b, Lyn, Syk, Btk, and BLNK gene accumulation, which exhibited positive interactions. We further verified that the mRNA expression of these genes was significantly upregulated and consistent with the RNA-seq results. These results suggest a role of these genes in the increase of B cells in the thymus of PIL mice. In summary, our results showed the changes in the thymus in PIL and elucidated the immunologic abnormalities of increased B cells, potentially providing insight into the associated molecular mechanisms and facilitating further research.

对 pristane 诱导的狼疮 (PIL) 小鼠的胸腺变化和发病机制的潜在机制知之甚少。本研究旨在系统和具体地检查胸腺的变化以及导致 PIL 小鼠免疫异常的潜在机制。结果表明，PIL小鼠表现出严重的胸腺增生、胸腺指数升高、组织病理学结构受损和胸腺细胞凋亡增加。我们发现胸腺 T 细胞分化受损，因为 CD4 ⁺ CD8 ⁺双阳性 (DP) 胸腺细胞频率显着降低，诱导后 28 周几乎不存在，而 CD4 CD8 ^-双阴性 (DN) 胸腺细胞和 CD4 ⁺ CD8 ^-单阳性 (CD4 ⁺ SP) 和 CD4 CD8 ⁺单阳性 (CD8 ⁺ SP) 细胞增加。这种现象可以通过抑制 DN 到 DP 细胞的转变和刺激 DP 细胞转化为 CD4 ⁺ /CD8 ⁺ SP 胸腺细胞来解释。此外，我们发现胸腺 B 细胞显着异常增加，这与CD19、Irf8、Ebf1、Pax5、Irf4、Blk、CXCL13、CXCR5、CD79a、CD79b、Lyn、Syk、Btk和BLNK 相关基因积累，表现出积极的相互作用。我们进一步验证了这些基因的 mRNA 表达显着上调并与 RNA-seq 结果一致。这些结果表明这些基因在增加 PIL 小鼠胸腺中 B 细胞中的作用。总之，我们的研究结果显示了 PIL 中胸腺的变化，并阐明了 B 细胞增加的免疫异常，可能提供对相关分子机制的深入了解并促进进一步研究。