Disease relevance of FCGR2C

• It suggests that dysregulation of FCGR2B may play a role in tumor progression in follicular lymphoma [1].
• The use of surface plasmon resonance imaging allowed the real time detection of differential interactions between Morbillivirus nucleoproteins and FcgammaRIIb (CD32) [2].
• Human monocyte-derived DCs that endocytosed tetanus toxoid (TT)-containing IgG liposomes via CD32 stimulated CD4(+) T cells more strongly than DCs pulsed with TT-containing bare liposomes or with soluble TT [3].
• CD32-mediated suppression of plasma cells in patients with multiple myeloma [4].

High impact information on FCGR2C

• We conclude that CD32 is an antigen uptake receptor on pDCs and that antigen presentation by pDCs is of particular relevance when circulating antibodies are present [5].
• To investigate possible structural and functional heterogeneity among these receptors, we have now isolated two additional cDNAs (hFcRII-B and hFcRII-C) from a human placental library, placenta being a good source of FcR-bearing macrophages and epithelial cells [6].
• However, the blots--as well as in situ hybridization and immunohistochemistry--demonstrated that hFcRII-C (along with a second monocyte marker, the c-fms encoded CSF-1 receptor) was expressed in placental syncytiotrophoblasts [6].
• Neutrophil responsiveness to IgG, as determined by fixed ratios of mRNA levels for activating and inhibitory FcgammaRII (CD32), is stable over time and unaffected by cytokines [7].
• We found a strong association between the 2B.4 haplotype of the FCGR2B promoter with increased transcriptional activity in individuals with 1:1 ratios and the more common low-expression 2B.1 haplotype in individuals with FcgammaRIIa/FcgammaRIIb2 mRNA ratios of 2:1, 3:1, or 4:1 [7].

Biological context of FCGR2C

• Stable transfection experiments enabled us to determine a unique binding pattern of anti-CD32 monoclonal antibodies to FcgammaRIIc [8].
• We have utilized these data to characterize a linked set of three coding region SNPs in the FcgammaRIIC exon 3 (EC1) that includes the stop codon SNP, which provides an important insight into natural killer cell function [9].
• Variation in human FCGR2C gene copy number [10].
• An in vitro study showed that intact immunoglobulin, but not F(ab')(2) fragments, suppressed the lipopolysaccharide-induced interleukin-1beta production associated with the downregulation of CD32 antigen (Fcgamma receptor II) expression [11].

Anatomical context of FCGR2C

• These data show that certain individuals express high levels of functional FcgammaRIIc isoforms on their NK cells [8].
• While the ectodomain of hFcRII-C was identical to hFcRII-B, its cytoplasmic tail was unrelated but highly homologous to the corresponding domain of the receptor isoform (mFcRII-B2) found in murine macrophages [6].
• Immunoprecipitation studies of FcgammaRIIc isoforms expressed in Jurkat cells revealed a protein of around 40 kDa for FcgammaRIIc1, and a protein of around 32 kDa for FcgammaRIIc3 [12].
• We hypothesized that neonatal B cells would be less susceptible to feedback inhibition by antibody, either through the expression of activation-competent FcgammaRII isoforms (FcgammaRIIa and FcgammaRIIc) or through reduced expression of the inhibitory FcgammaRIIb isoforms [13].
• The efficiency of FcalphaR-triggered granulocyte effector functions was comparable to that of FcgammaRIIa (CD32), as shown in experiments with bispecific antibodies [14].

Associations of FCGR2C with chemical compounds

• At the optimal PMA dose, the time of mRNA stimulation of CD32A and C mRNA varies and the addition of CX to U937 cells together with PMA enhanced the levels of CD32C mRNA but had no effect on CD32A mRNA levels [15].
• The addition of actinomycin D (ActD), a transcriptional inhibitor, together with either PMA or IFN-gamma diminishes the enhanced levels of CD32C mRNA to the basal levels, indicating that transcriptional regulation is involved in this modulatory process [15].

Regulatory relationships of FCGR2C

• Molecular characterization of FcgammaRIIc isoforms expressed by the CD32+ donors revealed that the majority of donors expressed the FcgammaRIIc1 isoform [16].
• The PMA and IFN-gamma stimulated CD32C mRNA is degraded within 2 hr post-stimulation and this degradation is delayed by the inhibition of de novo protein synthesis [15].

Other interactions of FCGR2C

• There are three different genes coding for Fc gamma RII: Fc gamma RIIA, Fc gamma RIIB and Fc gamma RIIC [17].
• We have analyzed the expression pattern and allelic polymorphisms of three FcgammaR genes (FcgammaRIIA, FcgammaRIIC and FcgammaRIIIA) in a large sample of RA patients and normal donors [18].
• These results demonstrate that the presence of multiple allelic polymorphisms in the FcgammaRIIC gene determine the expression and function of CD32 on NK cells [16].
• In this study, we investigated the effects of PMA and interferon-gamma (IFN-gamma) on the expression of CD32C mRNA in U937 cells [15].
• In one recent study, 21 individuals whose neutrophils lack Fc gamma RIIIb were found to be missing the entire Fc gamma RIIIB and Fc gamma RIIC genes [19].

Analytical, diagnostic and therapeutic context of FCGR2C

• FcgammaRIIa was consistently detected along with FcepsilonRI at the mRNA and protein levels; FcgammaRIIc was sometimes detected only by RT-PCR; but FcgammaRIIb, FcgammaRI, and FcgammaRIII mRNA and protein were not detected [20].

References