Fc Receptor Stable Cell Lines

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• Fc-FcγR and Fc-FcRn Binding Affinity Evaluation

  GenScript offers FcγRs and FcRn overexpression cell lines with binding capabilities spanning all IgG subclasses. These cell lines are designed for cell-based binding assays to evaluate Fc-FcγR and Fc-FcRn binding affinity.

  Following binding with the Fc region of antibodies that are attached to pathogens or infected cells, FcγRs can mediate effector functions including antibody-dependent cellular phagocytosis (ADCP) or antibody-dependent cell-mediated cytotoxicity (ADCC). During Fc engineering in antibody based drug development, increasing or decreasing Fc-FcγR binding affinity could potentially strengthen or weaken effector functions. FcRn involves in recycling of IgG type antibodies in serum, which increases the stability and half-life of antibodies. Hence, antibody Fc engineering for enhanced Fc-FcRn binding affinity could prolong the circulation half-life of antibody.

  

  Figure 1: Fc receptor expressing cells based binding assay with flow cytometer.
  Cell-based binding assay with flow cytometer is one of the accessible methods to evaluate binding affinity.

  Single-nucleotide polymorphism contributes to polymorphic FcγRs that can effect an individual’s immune response to antibody based drugs or immune therapies. Same antibody based drugs may have different efficiencies in patients with polymorphic FcγRs. GenScript offers polymorphic FcγRs overexpression cell lines for performing polymorphism studies.

  Table 1: Immunoglobulin subclass binding and functions of Human FcRγ and FcRn receptors.

  name	Alias	Polymorphism	IgG subclass binding	Function
  FcγRIIIa	CD16A	V158	Higher affinity to all human IgGs than F158	Activation /Inhibition
  		F158	Lower affinity to all human IgGs than V158	Activation /Inhibition
  FcγRIIIb	CD16B	-	IgG1,IgG3	Activation
  FcγRIIa	CD32A	H131	IgG1,IgG2,IgG3,IgG4	Activation /Inhibition
  		R131	lower affinity to IgG1 and IgG2 than H131, IgG3, IgG4	Activation /Inhibition
  FcγRIIb	CD32B	I232	IgG1,IgG2,IgG3,IgG4	Inhibition
  		T232	IgG1,IgG2,IgG3,IgG4	Inhibition
  FcγRIIc	CD32C	-	IgG1,IgG2,IgG3,IgG4	Activation
  FcγRI	CD64	-	IgG1,IgG3,IgG4	Activation
  FcRn	FcRn	-	IgG1,IgG2,IgG3,IgG4	Recycling, transport, uptake

• FcγRs and FcRn Structure

  The structure of Fc receptors effects their antibody binding affinity and their functions upon antibody binding. All of the FcγRs and FcRn overexpression cell lines provided by GenScript express the receptors mimicking the way they are present in their natural forms.

  The FcγRI, FcγRIIa, FcγRIIc and FcγRIIIa are primarily activating receptors, as they express immunoreceptor tyrosine activating motifs (ITAMs) 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.

  

  Figure 2: Schematic representation of human FcγRs and FcRn on cell surface

  Symbols: α (alpha chain), γ (gamma chain), ITAM (immunoreceptor tyrosine activating motifs), ITIM (immunoreceptor tyrosine inhibitory motif), β2m (β2-microglobulin)

• References
  1. 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 Therapyγ Int J Mol Sci. 2019;20(6). doi:10.3390/ijms20061379
  2. 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
  3. 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
  4. 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
  5. 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

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