Ocular Surface Center, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, TX, USA; Institute of Experimental Medicine (CONICET), National Academy of Medicine of Buenos Aires, Buenos Aires, Argentina.
Ocular Surface Center, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, TX, USA; Biochemistry and Cell Biology Graduate Program, Department of BioSciences, Rice University, Houston, TX, USA.
Clin Immunol. 2023 Mar;248:109251. doi: 10.1016/j.clim.2023.109251. Epub 2023 Feb 3.
Aging is a complex biological process in which many organs are pathologically affected. We previously reported that aged C57BL/6J had increased lacrimal gland (LG) lymphoid infiltrates that suggest ectopic lymphoid structures. However, these ectopic lymphoid structures have not been fully investigated. Using C57BL/6J mice of different ages, we analyzed the transcriptome of aged murine LGs and characterized the B and T cell populations. Age-related changes in the LG include increased differentially expressed genes associated with B and T cell activation, germinal center formation, and infiltration by marginal zone-like B cells. We also identified an age-related increase in B1 cells and CD19B220 cells. B220CD19 cells were GL7 (germinal center-like) and marginal zone-like and progressively increased with age. There was an upregulation of transcripts related to T follicular helper cells, and the number of these cells also increased as mice aged. Compared to a mouse model of Sjögren syndrome, aged LGs have similar transcriptome responses but also unique ones. And lastly, the ectopic lymphoid structures in aged LGs are not exclusive to a specific mouse background as aged diverse outbred mice also have immune infiltration. Altogether, this study identifies a profound change in the immune landscape of aged LGs where B cells become predominant. Further studies are necessary to investigate the specific function of these B cells during the aged LGs.
衰老是一个复杂的生物学过程，许多器官都会受到病理性影响。我们之前曾报道过，衰老的 C57BL/6J 小鼠泪腺（LG）中存在增多的淋巴样浸润，提示存在异位淋巴样结构。然而，这些异位淋巴样结构尚未得到充分研究。我们使用不同年龄的 C57BL/6J 小鼠分析了衰老小鼠 LG 的转录组，并对 B 细胞和 T 细胞群体进行了特征分析。LG 中的年龄相关变化包括与 B 和 T 细胞激活、生发中心形成和边缘区样 B 细胞浸润相关的差异表达基因增加。我们还发现 B1 细胞和 CD19+B220 细胞的数量随着年龄的增长而增加。B220+CD19+细胞为 GL7（生发中心样）和边缘区样，并且随着年龄的增长逐渐增加。与干燥综合征的小鼠模型相比，衰老 LG 的转录组反应具有相似性，但也有独特之处。此外，衰老 LG 中的异位淋巴样结构并不局限于特定的小鼠背景，因为衰老的不同品系近交系小鼠也存在免疫浸润。总之，这项研究确定了衰老 LG 中免疫景观发生了深刻变化，B 细胞成为优势细胞。需要进一步研究以探究这些 B 细胞在衰老 LG 中的具体功能。
