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Catalog Products » Other Products » Stable Cell Lines » Fc Receptor Cell Lines
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Fc Receptor Stable Cell Lines

Fc receptors (FcRs) are membrane proteins that bind with antibody Fc regions and help in regulating the body’s immune response. A variety of Fc receptors (Figure 1) selectively bind the Fc region of specific antibodies (Table 1) . When these antibodies are attached to disease-causing pathogens or infected cells, the Fc receptors can mediate their destruction by antibody-dependent cellular phagocytosis (ADCP) or antibody-dependent cell-mediated cytotoxicity (ADCC, Figure 2 ). The Fc region can also interact with complement proteins to induce complement-dependent cytotoxicity (CDC). The interaction of Fc receptors with complement proteins results in a wide range of modulated immune responses. Due to the central role of Fc receptors in regulating antibody function, binding kinetics of new antibodies may be tested using Fc receptor-expressing cell lines when developing antibody-based drugs and therapies.

Fc gamma receptors (FcγRs) (Figure 1) bind Immunoglobulin G antibodies (IgGs), and can enhance or inhibit IgG-based immune responses [1-5]. In the field of tumor biology and development of antibody therapies for cancer, the ADCC function of FcγRs has gained prominence. ADCC is initiated when FcγRs expressed on the surface of natural killer (NK) or other types of effector cells such as macrophages recognize and bind with the Fc domain of antibodies which are attached to the surface of tumor cells. The interaction with FcγRs (most often FcγRIIIA) with these bound antibodies releases perforins and granzymes from the effector cells, resulting in the lysis of the tumor cells (Figure 2). FcγRs make good targets for antibody-based therapies for cancers as they can assist in the destruction of diseased cells by ADCC [6]. Cell lines expressing FcγRs are often used to determine effectiveness of antibody drugs developed to treat various types of cancers and autoimmune diseases.

Some FcγRs have several polymorphic variants due to point mutations. The FcγR variant expressed by an individual can affect their chance of developing certain diseases such as SARS and ulcerative colitis, as well as the disease intensity (Table 1) [7-26]. FcγR variants can also determine a patient’s response to antibody-based drugs and therapies. Therefore, cell lines expressing FcγR polymorphisms are useful for developing personalized medicine.

Another type of Fc receptor, the neonatal Fc receptor (FcRn) is indicated in increasing the stability of antibodies and serum proteins such as albumins [27]. FcRn binds IgGs and albumins in a pH-dependent mechanism and mediates their transcytosis across polarized membranes [5]. FcRn is present in a variety of cells, including placental cells which transport IgGs from the mother to the developing fetus [24]. Cell lines expressing FcRn are useful screening tools to study transcytosis and in vitro clearance of antibody-based drugs.

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Figure 1. Human FcRγ and FcRn receptors.

This figure illustrates human FcRγ and FcRn receptors embedded in the cell membrane. The function of the FcRγ receptors is affected by their structures. The FcγRI, FcγRIIa, FcγRIIc and FcγRIIIa are primarily activating receptors, as they express immunoreceptor tyrosine activating motifs (ITAMs, brown circles) on their α or associated γ chains. On the other hand, the inhibitory receptor FcγRIIb expresses an immunoreceptor tyrosine inhibitory motif (ITIM). The FcγRIIIb receptor is a GPI-anchored protein which expresses neither ITAM nor ITIM motifs, but instead conducts signal transduction through associations with other Fc receptors. The FcRn receptor is structurally a heterodimer consisting of an α chain and a β2-microglobulin (β2m), both of which are important for the receptor’s expression on the cell surface, as well as for optimal IgG binding activity [3-5].

Table 1. Human FcRγ and FcRn receptors.

FcγRI FcγRIIa FcγRIIb FcγRIIc FcγRIIIa FcγRIIIb Neonatal Fc receptor
Alias
CD64 CD32A CD32B CD32C CD16A CD16B FcRn
Hypermorphism
- Histidine (H131) Arginine (R131) - - Valine (V158) Phenylalanine (F158) - -
Immunoglobulin subclass binding
IgG1,
IgG3,
IgG4		 IgG1,
IgG2,
IgG3,
IgG4		 IgG1,
IgG2 (lower affinity than H131),
IgG3,
IgG4		 IgG1,
IgG2 (low affinity),
IgG3,
IgG4		 IgG1,
IgG2 (low affinity),
IgG3,
IgG4		 Higher affinity to all human IgGs than F158 Lower affinity to all human IgGs than V158 IgG1,
IgG3		 IgG1,
IgG2,
IgG3,
IgG4
Expression
Monocytes, macrophages, neutrophils, dendritic cells, mast cells Basophils, eosinophils, monocytes, macrophages, neutrophils, dendritic cells, mast cells Basophils, eosinophils, monocytes, macrophages, neutrophils, dendritic cells, mast cells B-cells, basophils, dendritic cells, mast cells Natural Killer (NK) cells, monocytes, macrophages, neutrophils Natural Killer (NK) cells, monocytes, macrophages Natural Killer (NK) cells, monocytes, macrophages Neutrophils, basophils, eosinophils monocytes, macrophages, neutrophils, dendritic cells, endothelium, synctiotrophoblasts
Function
Activation Activation
/Inhibition		 Activation
/Inhibition		 Inhibition Activation Activation
/Inhibition		 Activation
/Inhibition		 Activation Recycling, transport, uptake
Link to diseases
- H131 variant is associated with less severe infection with encapsulated microorganisms including more severe SARS (Severe Acute Respiratory Syndrome) infection [7], Kawasaki disease [8], ulcerative colitis [9], Guillain–Barré syndrome [10]. R131 variant associated with more severe infection due to encapsulated microorganisms including SARS [7]; Immune thrombocytopenic purpura [11]; Systemic lupus erythematosus (SLE) [12]; IgA nephropathy [13,14] Lupus [12,15]; Atopy [16] Kawasaki Disease [17] Arthritis [18, 19]; Crohn’s disease [20] Arthritis [18, 19]; Crohn’s disease [20]; Systemic lupus erythematosus (SLE) [21]; Behçet's disease [22, 23] Wegener’s granulomatosis [24] -

FcRγ and FcRn alleles, immunoglobulin binding affinities, expression, function, and link to diseases [7-24].

Figure 2. Antibody-dependent cellular cytotoxicity (ADCC).

This figure illustrates how the FcRγ receptors on natural killer (NK) cells mediate destruction of antibody-marked cancer cells by the process of ADCC [6].

Product list

Receptor Cell Line Cat.No.
CD16A CHO-K1/CD16A 158F
CHO-K1/CD16A 158V
CD16B CHO-K1/CD16B
CD32A CHO-K1/CD32A 131His
CD32B
CHO-K1/CD32B 232Thr
CD32C CHO-K1/CD32C 13Gln
CD64 CHO-K1/CD64
FcRn CHO-K1/FcRn
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  2. Ben Mkaddem S, Benhamou M, Monteiro RC. Understanding Fc Receptor Involvement in Inflammatory Diseases: From Mechanisms to New Therapeutic Tools. Front Immunol. 2019;10. doi:10.3389/fimmu.2019.00811
  3. Bournazos S, Gupta A, Ravetch JV. The role of IgG Fc receptors in antibody-dependent enhancement. Nature Reviews Immunology. 2020;20(10):633-643. doi:10.1038/s41577-020-00410-0
  4. Kara S, Amon L, Lühr JJ, Nimmerjahn F, Dudziak D, Lux A. Impact of Plasma Membrane Domains on IgG Fc Receptor Function. Front Immunol. 2020;11. doi:10.3389/fimmu.2020.01320
  5. Praetor A, Hunziker W. beta(2)-Microglobulin is important for cell surface expression and pH-dependent IgG binding of human FcRn. J Cell Sci. 2002;115(Pt 11):2389-2397. Doi: https://doi.org/10.1242/jcs.115.11.2389
  6. van Erp EA, Luytjes W, Ferwerda G, van Kasteren PB. Fc-Mediated Antibody Effector Functions During Respiratory Syncytial Virus Infection and Disease. Front Immunol. 2019;10. doi:10.3389/fimmu.2019.00548
  7. Yuan FF, Tanner J, Chan PKS, et al. Influence of FcγRIIA and MBL polymorphisms on severe acute respiratory syndrome. Tissue Antigens. 2005;66(4):291-296. doi:10.1111/j.1399-0039.2005.00476.x
  8. Onouchi Y, Ozaki K, Burns JC, et al. A genome-wide association study identifies three new risk loci for Kawasaki disease. Nat Genet. 2012;44(5):517-521. doi:10.1038/ng.2220
  9. Asano K, Matsushita T, Umeno J, et al. A genome-wide association study identifies three new susceptibility loci for ulcerative colitis in the Japanese population. Nat Genet. 2009;41(12):1325-1329. doi:10.1038/ng.482
  10. Pol W-L van der, Berg LH van den, Scheepers RHM, et al. IgG receptor IIa alleles determine susceptibility and severity of Guillain-Barré syndrome. Neurology. 2000;54(8):1661-1665. doi:10.1212/WNL.54.8.1661
  11. Carcao MD, Blanchette VS, Wakefield CD, et al. Fcgamma receptor IIa and IIIa polymorphisms in childhood immune thrombocytopenic purpura. Br J Haematol. 2003;120(1):135-141. doi:10.1046/j.1365-2141.2003.04033.x
  12. Tsang-A-Sjoe MWP, Nagelkerke SQ, Bultink IEM, et al. Fc-gamma receptor polymorphisms differentially influence susceptibility to systemic lupus erythematosus and lupus nephritis. Rheumatology (Oxford). 2016;55(5):939-948. doi:10.1093/rheumatology/kev433
  13. Qiao J, Al‐Tamimi M, Baker RI, Andrews RK, Gardiner EE. The platelet Fc receptor, FcγRIIa. Immunological Reviews. 2015;268(1):241-252. doi:https://doi.org/10.1111/imr.12370
  14. Tanaka Y, Suzuki Y, Tsuge T, et al. FcgammaRIIa-131R allele and FcgammaRIIIa-176V/V genotype are risk factors for progression of IgA nephropathy. Nephrol Dial Transplant. 2005;20(11):2439-2445. doi:10.1093/ndt/gfi043
  15. Kyogoku et al. Fcγ receptor gene polymorphisms in Japanese patients with systemic lupus erythematosus: Contribution of FCGR2B to genetic susceptibility. Arthritis & Rheumatism. 2002; https://onlinelibrary.wiley.com/doi/full/10.1002/art.10257
  16. Wu J, Lin R, Huang J, et al. Functional Fcgamma receptor polymorphisms are associated with human allergy. PLoS One. 2014;9(2):e89196. doi:10.1371/journal.pone.0089196
  17. van der Heijden J, Breunis WB, Geissler J, de Boer M, van den Berg TK, Kuijpers TW. Phenotypic variation in IgG receptors by nonclassical FCGR2C alleles. J Immunol. 2012;188(3):1318-1324. doi:10.4049/jimmunol.1003945
  18. Morgan AW, Griffiths B, Ponchel F, et al. Fcgamma receptor type IIIA is associated with rheumatoid arthritis in two distinct ethnic groups. Arthritis Rheum. 2000;43(10):2328-2334. doi:10.1002/1529-0131(200010)43:10<2328::AID-ANR21>3.0.CO;2-Z
  19. Lee YH, Ji JD, Song GG. Associations between FCGR3A polymorphisms and susceptibility to rheumatoid arthritis: a metaanalysis. J Rheumatol. 2008;35(11):2129-2135. doi:10.3899/jrheum.080186
  20. Moroi R, Endo K, Kinouchi Y, et al. FCGR3A-158 polymorphism influences the biological response to infliximab in Crohn’s disease through affecting the ADCC activity. Immunogenetics. 2013;65(4):265-271. doi:10.1007/s00251-013-0679-8
  21. Koene HR, Kleijer M, Swaak AJ, et al. The Fc gammaRIIIA-158F allele is a risk factor for systemic lupus erythematosus. Arthritis Rheum. 1998;41(10):1813-1818. doi:10.1002/1529-0131(199810)41:10<1813::AID-ART13>3.0.CO;2-6
  22. Gillis C, Gouel-Chéron A, Jönsson F, Bruhns P. Contribution of Human FcγRs to Disease with Evidence from Human Polymorphisms and Transgenic Animal Studies. Front Immunol. 2014;5:254. doi:10.3389/fimmu.2014.00254
  23. Li X, Gibson AW, Kimberly RP. Human FcR Polymorphism and Disease. In: Daeron M, Nimmerjahn F, eds. Fc Receptors. Current Topics in Microbiology and Immunology. Springer International Publishing; 2014:275-302. doi:10.1007/978-3-319-07911-0_13
  24. Kelley JM, Monach PA, Ji C, et al. IgA and IgG antineutrophil cytoplasmic antibody engagement of Fc receptor genetic variants influences granulomatosis with polyangiitis. Proc Natl Acad Sci U S A. 2011;108(51):20736-20741. doi:10.1073/pnas.1109227109
  25. Hasegawa M, Nishiyama C, Nishiyama M, et al. A novel -66T/C polymorphism in Fc epsilon RI alpha-chain promoter affecting the transcription activity: possible relationship to allergic diseases. J Immunol. 2003;171(4):1927-1933. doi:10.4049/jimmunol.171.4.1927
  26. Hirunsatit R, Kongruttanachok N, Shotelersuk K, et al. Polymeric immunoglobulin receptor polymorphisms and risk of nasopharyngeal cancer. BMC Genet. 2003;4:3. doi:10.1186/1471-2156-4-3
  27. Bequignon E, Dhommée C, Angely C, et al. FcRn-Dependent Transcytosis of Monoclonal Antibody in Human Nasal Epithelial Cells In Vitro: A Prerequisite for a New Delivery Route for Therapy? Int J Mol Sci. 2019;20(6). doi:10.3390/ijms20061379
  28. Pyzik M, Sand KMK, Hubbard JJ, Andersen JT, Sandlie I, Blumberg RS. The Neonatal Fc Receptor (FcRn): A Misnomer? Front Immunol. 2019;10. doi:10.3389/fimmu.2019.01540