C8b-KO Mouse

C8b, the gene encoding the beta chain of the eighth component of human complement, is crucial for the function of the complement system. The complement system is involved in host defense, homeostasis, and tissue regeneration, bridging the innate and adaptive immune systems [2]. C8 is a serum protein consisting of three chains (alpha, beta, and gamma) encoded by C8A, C8B, and C8G respectively. In serum, the C8b-encoded beta-subunit binds non-covalently to the disulfide-linked alpha-gamma subunit [4].

In HBV-related hepatocellular carcinoma (HCC) patients, C8B expression levels have protective effects on overall survival (OS) and recurrence-free survival (RFS). High levels of C8B contribute to favorable OS and RFS, even after adjusting for clinicopathological characteristics [1]. A patient with combined heterozygous genetic variations in C2 and C8B presented with a reduced general condition and multiple autoimmune diseases. Functional investigations showed slightly impaired neutrophil and monocyte functionality, diminished C5aR1 expression, and declined activation potential of the alternative and classical complement pathways [2]. A young woman with a pathogen mutation in the C8B gene had recurrent meningococcal infections, and the investigation of her complement system showed no function of the terminal pathway [3].

In conclusion, C8b is essential for the normal function of the complement system. Its role in diseases such as HBV-related HCC, autoimmune diseases, and recurrent meningococcal infections has been revealed through genetic studies. Understanding the function of C8b in these disease conditions can provide insights into disease mechanisms and potentially guide treatment strategies.

References:

1. Zhang, Yuan, Chen, Xiaorong, Cao, Yajuan, Yang, Zongguo. 2021. C8B in Complement and Coagulation Cascades Signaling Pathway is a predictor for Survival in HBV-Related Hepatocellular Carcinoma Patients. In Cancer management and research, 13, 3503-3515. doi:10.2147/CMAR.S302917. https://pubmed.ncbi.nlm.nih.gov/33911900/

2. Mannes, Marco, Halbgebauer, Rebecca, Wohlgemuth, Lisa, Nilsson Ekdahl, Kristina, Huber-Lang, Markus. 2023. Combined Heterozygous Genetic Variations in Complement C2 and C8B: An Explanation for Multidimensional Immune Imbalance? In Journal of innate immunity, 15, 412-427. doi:10.1159/000528607. https://pubmed.ncbi.nlm.nih.gov/36858027/

3. Andersen, Ulrik Ørsø, Bay, Jakob Thaning, Jensen, Lise Heilmann. . [Recurrent meningococcal infection in a young woman witha mutation in the C8B gene]. In Ugeskrift for laeger, 184, . doi:. https://pubmed.ncbi.nlm.nih.gov/35703060/

4. Kaufmann, T, Rittner, C, Schneider, P M. . The human complement component C8B gene: structure and phylogenetic relationship. In Human genetics, 92, 69-75. doi:. https://pubmed.ncbi.nlm.nih.gov/8365729/