Fc Receptor Cell Lines
Membrane protein stable cell lines are widely used in many areas of biomedical research. Creative Biolabs can offer membrane protein stable cell lines to stablish in vitro models for High Throughput Screening.
Creative Biolabs offers high-quality, innovative tools to help research groups accelerate membrane protein drug discovery. They can be found by targets. If there is no product that meets your needs, please contact us.
Background of Membrane Fc Receptor
The Fc receptor (short for crystallizable fragment receptor) is a heterodimer composed of type I MHC-associated molecules and β2 microglobulin with a high affinity for IgG and albumin protein. It is widely distributed in various types of phagocytes, granulocytes, or lymphocytes from the innate and adaptive immune systems. Fc receptor can help immune cells recognize pathogens by binding to surface antigens of foreign cells or microbial and have benefits in the protective functions of the immune system.
Fig.1 Structure Prediction of Human FCGR.1
Functions and Mechanisms of Membrane Fc Receptor
Fc receptor can mediate antibody recycling and IgG transmembrane transport, and enhance immune cell antigen presentation and a series of related immune response processes. Fc receptor mainly interacts with IgG and promotes its internalization and recycling process through a pH-dependent mechanism. In a neutral pH environment, the Fc receptor does not bind to IgG, but IgG can interact with its receptors in an acidic environment, thereby avoiding intracellular transport and subsequent degradation processes. The conjugates of IgG and Fc are subsequently separated from each other by exocytosis back out of the cell and exposure to neutral solutions. The IgG half-life is extended by the Fc-mediated recycling mechanism.
Applications and Pathology of Fc Cell Lines
The study of Fc cell lines can be used for drug design and development based on the interaction mechanism of Fc and IgG proteins, thereby prolonging the half-life of antibodies or realizing the transmembrane delivery of drugs. Besides, the activation of the Fc receptor stimulates phagocytic or cytotoxic cells to destroy microbes or infected cells by antibody-mediated phagocytosis or antibody-dependent cell-mediated cytotoxicity, therefore Fc receptor represents an ideal target for autoimmune diseases like Myasthenia gravis.
Published Data
| Paper Title | Differences between Human and Mouse IgM Fc Receptor |
| Journal | International Journal of Molecular Sciences |
| Published | 2021 |
| Abstract | IgM is the first immunoglobulin isotype that appears during ontogeny and immune system maturation. Two forms of IgM that differ in the C-terminus of the µ heavy chain have been validated: pre-immune naturally occurring IgM and antigen-induced immune IgM, both IgMs are important for regulating self-antigens and immune responses against pathogen invasion. Functional cloning studies have successfully identified and studied the genetic and protein profiles, and important roles of Fc receptors in the IgM effector-mediated immune system. In this study, the researchers focused on recent analyzes of FcµR mutations to describe differences in ligand binding activity, cellular distribution, and recognition processes between human and mouse FcµRs. |
| Result |
Previous studies have shown that the human and mouse FcµRs are adjacent to the genetic locations of two other IgM-binding receptors, pIgR, and Fcα/µR, both in syntenic regions on chromosome 1. But in this experiment, the large difference between the two receptors in terms of ligand binding potential, cellular distribution, and recognition process was verified. Through the difference in IgM binding between human and mouse FcµR, the researchers identified three key sites in the IgM recognition and binding process of human FcµR, including Asn109 in CDR3, Asn66 in CDR2 and Lys79 to Arg83 in the DE loop. Modeling analysis and structural calculations also yielded the same results as the mutation data. Even more surprisingly, when these three residues were used to replace the corresponding mouse residues, the resulting mouse FcµR triple mutants constitutively bound to IgM like the human receptor. This finding confirms that these three critical sites are essential components of human FcµR and IgM to form constitutive IgM-ligands. In addition, the researchers found that replacing Glu41 and Met42 in CDR1 of human FcµR with mouse equivalents Gln and Leu can significantly enhance receptor expression and IgM binding, and this phenomenon will also be increased when two equivalent replacements are administered simultaneously. These findings will aid in the future development of FcµR-targeted preventive and therapeutic interventions and advance understanding of the immune effects of IgM.
|
Fig. 2 IgM binding of human/mouse chimeric FcµRs.2,3
References
- Image retrieved from Alphafold (Uniprot ID P08101), used under CC BY 4.0, without any modification.
- Kubagawa, Hiromi, et al. "Differences between human and mouse IgM Fc receptor (FcµR)." International Journal of Molecular Sciences 22.13 (2021): 7024.
- Image retrieved from Figure 3 " IgM binding of human/mouse chimeric FcµRs. " Kubagawa, et al. 2021, used under CC BY 4.0. The original image was modified by extracting and the title was changed to " IgM binding of human/mouse chimeric FcµRs.".
