New CHO cell line variants, expressing different classes of Fc gamma receptors (FcγRs) have been deposited exclusively into the ECACC General Collection by Cambridge Enterprise Limited, UK. The variant lines were developed in the laboratory of Dr. Mike Clark at Cambridge University and include five cell lines that express three different human FcγRs including allotypes of FcγRIIa and FcγRIIIa (Table 1)1,2.
Cell line Name Catalogue Number |
Human Fcγ Receptor Expression |
CHO-K1.Cl-0204 |
FcγRIIa Fc gamma receptor 2A, 131R |
CHO-K1.Cl-0205 |
FcγRIIa Fc gamma receptor 2A, 131H |
CHO-K1.Cl-0206 |
FcγRIIb Fc gamma receptor 2b |
CHO-K1.Cl6 |
FcγRIIIa Fc gamma receptor 3A, 158V |
CHO-K1.Cl7 |
FcγRIIIa Fc gamma receptor 3A, 158F |
Table 1:ECACC exclusive CHO variant cell lines expressing human Fc gamma receptors
The Fcγ receptor family are expressed on the surface of hematopoietic cells and are involved in regulating immune responses through activating or inhibitory signals3. The Fc domains of the four subclasses of immunoglobulin G (IgG1, IgG2, IgG3 and IgG4) bind to FcγRs with varying affinities (Table 2). Formation of Fc-FcγR complexes initiates a number of immunological responses including antibody dependent cell mediated cytotoxicity and phagocytosis4,5.
Cell Type |
Human Fcγ Receptor Expression |
||
FcγRIIa |
FcγRIIb |
FcγRIIIa |
|
B-cells |
− |
+ |
− |
T cells |
− |
− |
− |
NK cells |
− |
− |
+ |
Dendritic cells |
+ |
+ |
− |
Macrophages/Monocytes |
+ |
+ |
+ |
Neutrophils |
+ |
− |
+ |
Eosinophils |
+ |
− |
− |
Platelets |
+ |
− |
− |
Table 2: Human Fc gamma receptor expression in hematopoietic cells3
Antibody based therapies are used to treat a number of cancers and autoimmune diseases and their effectiveness, in part, depends on the binding affinity of IgG antibodies and FcγRs. Polymorphisms in the genes encoding for the FcγRs can affect a patient’s response to antibody and immunoglobulin therapy. Examples of such variances in individual responses have been reported in the literature. Treatment of non-Hodgkin lymphomas with Rituximab has been shown to be more effective in homozygous FCGR3A-158V patients compared with heterozygous FCGR3A-158F carriers6. In addition, FCGR gene polymorphisms have also been identified as a risk factor for a number of immunological diseases (Table 3). Thus, FcγRs influence both disease progression and therapeutic response in patients.
Gene |
Receptor |
Single Nucleotide Polymorphism |
Disease |
FCGR2A |
FcγRIIa |
R131 |
|
H131 |
|
||
FCGR3A |
FcγRIIIa |
V158 |
|
F158 |
|
Table 3: Diseases associated with Fc gamma receptor polymorphisms7
Fc gamma receptors are proving to be useful targets for the treatment of autoimmune diseases and cancer. Understanding the biophysical interactions between the receptors and IgG antibodies is aiding the development of more personalised and effective therapies. The FcγR expressing CHO cell lines from ECACC offer researchers a novel easy to access in vitro model for better understanding of receptor function and provide a novel tool for use in antibody-based drug discovery and development.
References
February 2017
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