Differential expression of Fcγ RIIA, Fcγ RIIB and Fcγ RIIC in hematopoietic cells: Analysis of transcripts

Cassel, Diana L.; Keller, Margaret; Surrey, Saul; Schwartz, Elias; Schreiber, Alan D.; Rappaport, Eric; McKenzie, Steven E.

doi:10.1016/0161-5890(93)90113-p

Cited by 110 publications

(69 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On which cells and through which receptor (FcgRIIB-1 or -2) the modulation is occurring is the subject of our ongoing studies. Previously, it has been reported that the FcgRIIB-1 isoform, expressed predominantly on B cells, does not internalize, whereas the FcgRIIB-2 isoform expressed on macrophages and DCs does (51,52). However, in our in vitro and in vivo experiments we noted clear modulation of the surface-bound mAb and receptor in both normal and malignant B cells as well as macrophages and confirmed the expected expression pattern of FcgRIIB isoforms in these cells.…”

Section: Cd19crecontrasting

confidence: 30%

Immunotherapy Targeting Inhibitory Fcγ Receptor IIB (CD32b) in the Mouse Is Limited by Monoclonal Antibody Consumption and Receptor Internalization

Williams

Tutt²,

Beers

et al. 2013

The Journal of Immunology

View full text Add to dashboard Cite

Genetic deficiency of the inhibitory Fc receptor, FcγRIIB (CD32b), has been shown to augment the activity of activatory FcγR and promote mAb immunotherapy. To investigate whether mAbs capable of blocking FcγRIIB have similar capacity, we recently generated a panel of specific anti-mouse FcγRIIB mAbs that do not cross-react with other FcRs, allowing us to study the potential of FcγRIIB as a therapeutic target. Previous work revealed a number of these mAbs capable of eliciting programmed cell death of targets, and in the present study we demonstrated their ability to promote target cell phagocytosis. However, in a variety of murine tumor models, anti-FcγRIIB mAbs demonstrated limited therapeutic activity despite optimized treatment regimens. Unexpectedly, we observed that the anti-FcγRIIB mAbs are rapidly and extensively consumed in vivo, both by the tumor and host cells, including B cells, leading to a precipitous loss from the circulation. Closer analysis revealed that the anti-FcγRIIB mAbs become extensively internalized from the cell surface within 24 h in vivo, likely explaining their suboptimal efficacy. Subsequent studies revealed that anti-FcγRIIB mAb immunotherapy was effective when used against FcγRIIB+ tumors in FcγRIIB−/− recipients, indicating that consumption of the mAb by nontumor cells is the primary limitation of these reagents. Importantly, similar rates of internalization were not seen on human target cells, at least in vitro. These studies further highlight the need to determine the propensity of mAb therapeutics to internalize target receptors and also identify potential key differences between human and mouse cells in this respect.

show abstract

Section: Cd19crecontrasting

confidence: 30%

Immunotherapy Targeting Inhibitory Fcγ Receptor IIB (CD32b) in the Mouse Is Limited by Monoclonal Antibody Consumption and Receptor Internalization

Williams

Tutt²,

Beers

et al. 2013

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Fc␥RIIA, -B, and -C receptors (expressed from the -A, -B, and -C genes) all show high homology in the extracellular and transmembrane regions, and B-cells can co-express diverse receptor isoforms (a1-a3; b1-b2; c1-c4) as a consequence of alternative splicing of Fc␥RIIA, -B, or -C mRNA (32,33). To characterize Fc␥RII expression in B593, RT-PCR was performed by using primers that could distinguish Fc␥RIIA͞C from Fc␥RIIB cDNA (Fig.…”

Section: Southern Blot Analysis and Cloning Of The T(1;22)(q21;q11) Bmentioning

confidence: 99%

The IgG Fc receptor, FcγRIIB, is a target for deregulation by chromosomal translocation in malignant lymphoma

Callanan

Baccon

Mossuz

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Rearrangement of chromosomal bands 1q21–23 is one of the most frequent chromosomal aberrations observed in hematological malignancy. The genes affected by these rearrangements remain poorly characterized. Typically, 1q21–23 rearrangements arise during tumor evolution and accompany disease-specific chromosomal rearrangements such as t(14;18) ( BCL2 ) and t(8;14) ( MYC ), where they are thus thought to play an important role in tumor progression. The pathogenetic basis of this 1q21–23-associated disease progression is currently unknown. In this setting, we surveyed our series of follicular lymphoma for evidence of recurring 1q21–23 breaks and identified three cases in which a t(14;18)(q32;q21) was accompanied by a novel balanced t(1;22)(q22;q11). Molecular cloning of the t(1;22) in a cell line (B593) derived from one of these cases and detailed fluorescent in situ hybridization mapping in the two remaining cases identified the FCGR2B gene, which encodes the immunoreceptor tyrosine-based inhibition motif-bearing IgG Fc receptor, FcγRIIB, as the target gene of the t(1;22)(q22;q11). We demonstrate deregulation of FCGR2B leading to hyperexpression of FcγRIIb2 as the principal consequence of the t(1;22). This is evidence that IgG Fc receptors can be targets for deregulation through chromosomal translocation in lymphoma. It suggests that dysregulation of FCGR2B may play a role in tumor progression in follicular lymphoma.

show abstract

“…There is no sequence information about the 5′ portion of Fc␥RIIB and Fc␥RIIC that can be used to distinguish the two genes and to gain insight into the very distinct cell type specific expression patterns. [26][27][28] Therefore, we sequenced 3.4 kb of the 5′ promoter, as well as the complete first (7 kb) and second (1 kb) introns of both Fc␥RIIB and Fc␥RIIC using our BAC clones containing either Fc␥RIIB or Fc␥RIIC. A schematic representation of the sequence variations between the two genes in the 5′ portion is shown in Figure 2.…”

Section: Resultsmentioning

confidence: 99%

Genomic organization of classical human low-affinity Fcγ receptor genes

Edberg

et al. 2002

Genes Immun

View full text Add to dashboard Cite

show abstract

Differential expression of Fcγ RIIA, Fcγ RIIB and Fcγ RIIC in hematopoietic cells: Analysis of transcripts

Cited by 110 publications

References 24 publications

Immunotherapy Targeting Inhibitory Fcγ Receptor IIB (CD32b) in the Mouse Is Limited by Monoclonal Antibody Consumption and Receptor Internalization

Immunotherapy Targeting Inhibitory Fcγ Receptor IIB (CD32b) in the Mouse Is Limited by Monoclonal Antibody Consumption and Receptor Internalization

The IgG Fc receptor, FcγRIIB, is a target for deregulation by chromosomal translocation in malignant lymphoma

Genomic organization of classical human low-affinity Fcγ receptor genes

Contact Info

Product

Resources

About