Morimoto Keiko, Sano Hitomi, Takahashi Michiko, Takahashi Rikuo, Nakajima Kazunori
Department of Anatomy, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
J Neuroinflammation. 2025 Jun 9;22(1):153. doi: 10.1186/s12974-025-03457-9.
Immunoglobulin (Ig) is a critical molecule in the body's defense against foreign substances such as bacteria and viruses. While traditionally considered B cell specific, studies have reported that Ig is also expressed by non-B cells. However, it is not known to what extent Ig is expressed in the brain and which type of variable regions are expressed. In this study, we elucidated the expression profile of Igs from embryonic to adult stages using single-cell RNA sequencing data and Ig repertoire analysis. Our results revealed that microglia express Ighm transcripts from embryonic to adult stages. These transcripts contain the upstream region of the Ighj region. In addition, Ighm is expressed in the layer 6 corticothalamic neurons, some of which co-express Ighg2c in the adult brain. In particular, we were able to generate a comprehensive profile of Ig variable region expression from embryonic to adult stages. Furthermore, the response of Ighm expression in microglia to lipopolysaccharide is markedly different from that in B cells, suggesting a novel, brain-specific role for the Ig gene, distinct from its classical function in the immune system.
免疫球蛋白（Ig）是机体抵御细菌和病毒等外来物质的关键分子。虽然传统上认为Ig是B细胞特异性的，但研究报告称非B细胞也表达Ig。然而，目前尚不清楚Ig在大脑中的表达程度以及表达哪种类型的可变区。在本研究中，我们利用单细胞RNA测序数据和Ig库分析阐明了从胚胎期到成年期Ig的表达谱。我们的结果显示，小胶质细胞从胚胎期到成年期都表达Ighm转录本。这些转录本包含Ighj区域的上游区域。此外，Ighm在6层皮质丘脑神经元中表达，其中一些在成年大脑中共同表达Ighg2c。特别是，我们能够生成从胚胎期到成年期Ig可变区表达的全面图谱。此外，小胶质细胞中Ighm表达对脂多糖的反应与B细胞明显不同，这表明Ig基因具有一种新的、大脑特异性的作用，与其在免疫系统中的经典功能不同。
