C1qb, a component of the complement C1q complex, plays a crucial role in the activation of the classical complement pathway. The classical complement pathway is involved in various biological processes such as immune defense, inflammation regulation, and clearance of apoptotic cells. Dysregulation of this pathway can lead to various diseases [1-10].

In primary refractory diffuse large B cell lymphoma, an increased proportion of C1QB-expressing macrophages was found in patients with progressive disease before CAR-T cell therapy. Cholesterol efflux from these macrophages inhibited CAR-T cells' cytotoxicity by inducing an immunosuppressive state in CD8+ T cells, leading to their exhaustion [1]. In colorectal cancer, forward MR analysis demonstrated that C1QB was a risk factor for CRC, suggesting an oncogenic role [2]. In skin cutaneous melanoma, high levels of C1QB expression were associated with favorable prognosis [3,8]. In type 1 diabetes mellitus, C1QB may be a key gene affecting macrophages in the pancreatic islet immune microenvironment, and silencing C1QB inhibited the differentiation of monocytes into macrophages, reduced the number of macrophages, and alleviated pancreatic islet β-cell damage [4]. In diabetic nephropathy, C1QB was identified as a potential candidate gene for diagnosis [5]. In intrahepatic cholangiocarcinoma, an APOE+C1QB+ macrophage subtype was identified, which contributed to a poor prognosis [6]. In psoriasis complicated with atherosclerosis, C1QB was identified as an important hub gene [7].

In conclusion, C1qb is essential for the classical complement pathway and is involved in multiple diseases. Studies using various models, though not specifically KO/CKO mouse models in the provided references, have revealed its role in cancer, diabetes-related complications, and immune-related diseases, highlighting its potential as a therapeutic target in these disease areas.

References:

1. Yan, Zi-Xun, Dong, Yan, Qiao, Niu, Sheng, Ling-Shuang, Zhao, Wei-Li. 2024. Cholesterol efflux from C1QB-expressing macrophages is associated with resistance to chimeric antigen receptor T cell therapy in primary refractory diffuse large B cell lymphoma. In Nature communications, 15, 5183. doi:10.1038/s41467-024-49495-4. https://pubmed.ncbi.nlm.nih.gov/38890370/

2. Jiao, Mingwen, Cui, Yuying, Qiu, Xiaodong, Guo, Congcong, Tian, Hu. 2024. Causal relationship between complement C1QB and colorectal cancer: a drug target Mendelian randomization study. In Frontiers in genetics, 15, 1403509. doi:10.3389/fgene.2024.1403509. https://pubmed.ncbi.nlm.nih.gov/39109334/

3. Liang, Zhuoshuai, Pan, Lingfeng, Shi, Jikang, Zhang, Lianbo. 2022. C1QA, C1QB, and GZMB are novel prognostic biomarkers of skin cutaneous melanoma relating tumor microenvironment. In Scientific reports, 12, 20460. doi:10.1038/s41598-022-24353-9. https://pubmed.ncbi.nlm.nih.gov/36443341/

4. Ji, Lili, Guo, Wei. 2022. Single-cell RNA sequencing highlights the roles of C1QB and NKG7 in the pancreatic islet immune microenvironment in type 1 diabetes mellitus. In Pharmacological research, 187, 106588. doi:10.1016/j.phrs.2022.106588. https://pubmed.ncbi.nlm.nih.gov/36464147/

5. Hu, Yongzheng, Yu, Yani, Dong, Hui, Jiang, Wei. 2023. Identifying C1QB, ITGAM, and ITGB2 as potential diagnostic candidate genes for diabetic nephropathy using bioinformatics analysis. In PeerJ, 11, e15437. doi:10.7717/peerj.15437. https://pubmed.ncbi.nlm.nih.gov/37250717/

6. Bao, Xuanwen, Li, Qiong, Chen, Jinzhang, Zhao, Peng, Ruan, Jian. . Molecular Subgroups of Intrahepatic Cholangiocarcinoma Discovered by Single-Cell RNA Sequencing-Assisted Multiomics Analysis. In Cancer immunology research, 10, 811-828. doi:10.1158/2326-6066.CIR-21-1101. https://pubmed.ncbi.nlm.nih.gov/35604302/

7. Su, Wenxing, Zhao, Ying, Wei, Yuqian, Ji, Jiang, Yang, Shun. 2021. Exploring the Pathogenesis of Psoriasis Complicated With Atherosclerosis via Microarray Data Analysis. In Frontiers in immunology, 12, 667690. doi:10.3389/fimmu.2021.667690. https://pubmed.ncbi.nlm.nih.gov/34122426/

8. Yang, Huanglong, Che, Dehui, Gu, Yuxiang, Cao, Dongsheng. 2022. Prognostic and immune-related value of complement C1Q (C1QA, C1QB, and C1QC) in skin cutaneous melanoma. In Frontiers in genetics, 13, 940306. doi:10.3389/fgene.2022.940306. https://pubmed.ncbi.nlm.nih.gov/36110204/