Affinage

FCGR2B

Low affinity immunoglobulin gamma Fc region receptor II-b · UniProt P31994

Length
310 aa
Mass
34.0 kDa
Annotated
2026-06-09
100 papers in source corpus 27 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FcγRIIB (CD32B) is the inhibitory IgG Fc receptor that sets thresholds for immune-cell activation and tolerance, principally by co-clustering with activating immunoreceptors and dampening their downstream signaling (PMID:9242674, PMID:31036800). Upon co-ligation with the B-cell antigen receptor, Kit, or other activating receptors, its phosphorylated ITIM recruits the inositol 5'-phosphatase SHIP rather than SHP-1; SHIP hydrolyzes PIP3, blocking Akt activation, calcium influx, and CD19 phosphorylation despite intact PI3K activity (PMID:9242674, PMID:10224144, PMID:12217398). This SHIP-dependent module suppresses BCR-driven BLyS survival signaling, mast-cell proliferation and degranulation, and antigen-independent human B-cell responses through Btk and p38 MAPK (PMID:12217398, PMID:18791164, PMID:26475492, PMID:29138419). The receptor's transmembrane domain independently tunes function: the SLE-associated I232T polymorphism tilts the TM helix, bending the ectodomain toward the membrane to allosterically reduce IgG binding affinity, while also altering ITIM-independent inhibition of BCR signaling (PMID:14613290, PMID:31343409). FcγRIIB output is governed at the expression level through promoter polymorphisms that alter transcription-factor binding and receptor abundance (PMID:12370366, PMID:15153543), and post-translationally by TLR4-induced MARCH3-mediated ubiquitination and downregulation (PMID:26694610). Beyond canonical inhibition, FcγRIIB acts as a pro-apoptotic and signaling receptor in multiple contexts: crosslinking eliminates bone-marrow plasma cells, plasmablasts, and myeloma cells, and engagement of the functional ligand FGL2 induces caspase-3/7 apoptosis in B cells and effector CD8+ T cells independently of IgG (PMID:17322888, PMID:18991288, PMID:31940267). It restrains autoreactive B-cell selection within germinal centers, including on follicular dendritic cells and marginal-zone B cells (PMID:31036800, PMID:31775042, PMID:35819855), limits CD8+ T-cell responsiveness to PD-1/CTLA-4 checkpoint blockade in a cell-intrinsic Fc-dependent manner (PMID:37611081), and impairs therapeutic antibody-mediated target depletion by competing with activating FcγRs for Fc binding even without ITIM signaling (PMID:35858562). FcγRIIB additionally functions outside the immune system as an endothelial and neuronal receptor: it mediates CRP-driven PP2A inhibition of eNOS and hyposialylated-IgG impairment of insulin transcytosis driving insulin resistance (PMID:16269657, PMID:29202472), crosslinks with dectin-1 in a galactosylated-IgG-dependent manner to suppress complement signaling (PMID:22922409), and binds Aβ oligomers and α-synuclein fibrils on neurons to trigger ER stress, caspase-12, and SHP-1/SHP-2 activation (PMID:23921129, PMID:29298416).

Mechanistic history

Synthesis pass · year-by-year structured walk · 27 steps
  1. 1997 High

    Resolved which phosphatase executes FcγRIIB inhibition, establishing SHIP rather than SHP-1 as the effector recruited to the phosphorylated receptor in B cells.

    Evidence Co-IP of SHIP with FcγRIIB and calcium assays in SHP-1-deficient (motheaten) vs normal B cell lines

    PMID:9242674

    Open questions at the time
    • Did not define which kinase phosphorylates the ITIM
    • Did not establish the lipid substrate consumed by SHIP
  2. 1999 High

    Defined the biochemical mechanism downstream of SHIP, showing it consumes PIP3 to block Akt despite normal PI3K activity.

    Evidence PIP3 measurement and Akt kinase assays in A20 B cells with catalytic-dead SHIP and SHIP-null comparisons

    PMID:10224144

    Open questions at the time
    • Did not address SHIP-independent inhibitory branches
    • Restricted to B-cell context
  3. 2002 High

    Extended the inhibitory module beyond the BCR, showing FcγRIIB-SHIP suppresses Kit-driven mast cell proliferation and cell-cycle entry.

    Evidence Co-aggregation, cell cycle analysis, SHIP-null cells, and SHIP catalytic-domain chimeric receptors in mast cells

    PMID:12217398

    Open questions at the time
    • Identity of the residual SHIP-independent inhibition unresolved
  4. 2002 High

    Linked receptor abundance to autoimmunity, showing a promoter polymorphism abolishing AP-4 binding lowers FcγRIIB in germinal-center B cells and raises IgG responses.

    Evidence Luciferase reporters, EMSA, and NZB-allele congenic mice

    PMID:12370366

    Open questions at the time
    • Murine allele; human relevance addressed separately
    • Did not test causal link to overt autoantibody disease
  5. 2003 High

    Demonstrated that the transmembrane I232T/I187T polymorphism alters signaling independently of the ITIM, implicating the TM domain in receptor function.

    Evidence Reconstitution of allelic and ITIM-truncated constructs in FcγRIIB-negative B cells with CD19 phosphorylation and calcium assays

    PMID:14613290

    Open questions at the time
    • Structural basis of the TM effect not defined
    • Single lab
  6. 2004 Medium

    Identified a human promoter haplotype that raises FcγRIIB expression and associates with SLE susceptibility.

    Evidence Luciferase reporters in B and myeloid lines plus case-control genetics in 600 Caucasians

    PMID:15153543

    Open questions at the time
    • Single functional reporter method
    • Transcription factors mediating the difference not identified
  7. 2005 High

    Established a non-immune endothelial function, showing CRP signals via FcγRIIB to activate PP2A and blunt eNOS.

    Evidence PP2A siRNA, heterologous expression, and FcγRIIB KO mouse vascular conductance assays

    PMID:16269657

    Open questions at the time
    • Direct CRP-FcγRIIB binding affinity not quantified
    • Coupling between receptor and PP2A activation undefined
  8. 2007 High

    Revealed a pro-apoptotic role, showing FcγRIIB crosslinking eliminates plasma cells and that lupus plasma cells escape by losing the receptor.

    Evidence Crosslinking apoptosis assays in mouse and human plasma cells/myeloma and lupus-prone mouse comparison

    PMID:17322888

    Open questions at the time
    • Apoptotic signaling pathway not delineated
    • Endogenous ligand triggering apoptosis not identified here
  9. 2008 High

    Identified FGL2 as a direct FcγRIIB ligand mediating immunosuppression and DC tolerance.

    Evidence SPR binding, FcγRIIB-null cells, and skin allograft survival in KO mice

    PMID:18991288

    Open questions at the time
    • Binding interface on receptor and ligand not mapped
    • Downstream apoptotic effectors not defined here
  10. 2008 High

    Dissected cell-autonomous roles, showing B-cell FcγRIIB controls autoimmunity while macrophage FcγRIIB affects infection outcome.

    Evidence Cell-type-specific transgenic overexpression with arthritis, SLE, and S. pneumoniae models

    PMID:18362174

    Open questions at the time
    • Mechanism of macrophage-specific infection susceptibility unresolved
  11. 2008 Medium

    Connected FcγRIIB inhibition to B-cell survival, showing it dampens BLyS-receptor upregulation and downstream survival signals via SHIP1.

    Evidence B cell co-aggregation with SHIP1-deficient comparison and BLyS signaling readouts

    PMID:18791164

    Open questions at the time
    • Single lab
    • Mechanism linking SHIP1 to BLyS receptor expression indirect
  12. 2012 High

    Uncovered a glycan-dependent partnership with dectin-1 that suppresses complement-driven inflammation.

    Evidence Reciprocal Co-IP, SHIP/Syk phosphorylation, glycan-manipulated IgG1, and in vivo disease models

    PMID:22922409

    Open questions at the time
    • Stoichiometry of the FcγRIIB-dectin-1 complex unknown
    • Structural basis of galactose dependency undefined
  13. 2013 High

    Established FcγRIIB as a neuronal Aβ-oligomer receptor mediating Alzheimer's neurotoxicity.

    Evidence Aβ-FcγRIIB binding, KO neuron resistance, ER stress/caspase-12 assays, and LTP/memory rescue in AD mice

    PMID:23921129

    Open questions at the time
    • Signaling between receptor and ER stress not fully mapped
    • Relationship to ITIM/SHIP module in neurons unclear
  14. 2015 Medium

    Identified MARCH3 as the E3 ligase downregulating FcγRIIB after TLR4 activation, defining post-translational regulation.

    Evidence Ubiquitination assays and MARCH3 siRNA in LPS-treated monocytes

    PMID:26694610

    Open questions at the time
    • Single lab; ubiquitination site not mapped
    • Direct MARCH3-FcγRIIB interaction not shown
  15. 2015 Medium

    Showed FcγRIIB on monocytes is necessary and sufficient to crosslink the anti-CD28 superagonist TGN1412 and drive T-cell proliferation.

    Evidence Density-dependent FcγRIIB upregulation and monocyte/T-cell reconstitution in PBMC

    PMID:25395427

    Open questions at the time
    • Single lab
    • Mechanism of density-driven upregulation not defined
  16. 2015 Medium

    Defined antigen-independent inhibition of human B-cell subsets through Btk and p38 MAPK with subset-selective effects.

    Evidence Crosslinking on sorted human B cell subsets with Btk and p38 inhibitor dissection

    PMID:26475492

    Open questions at the time
    • Single lab
    • Relationship between Btk/p38 branch and SHIP branch unresolved
  17. 2016 Medium

    Linked CRP-FcγRIIB signaling to fibrosis via ERK/p38-Smad3-mTOR crosstalk.

    Evidence CRPtg-db/db mice, CD32b neutralizing antibody, Smad3 inhibitor, and Smad3-mTOR Co-IP

    PMID:27221338

    Open questions at the time
    • Single lab
    • Direct receptor-to-Smad3 coupling not biochemically defined
  18. 2017 High

    Extended endothelial signaling to metabolism, showing hyposialylated IgG-FcγRIIB impairs insulin transcytosis and causes insulin resistance.

    Evidence Endothelium-specific KO mice, HFD, IgG transfer, in vitro transcytosis, and T2DM patient IgG

    PMID:29202472

    Open questions at the time
    • Intracellular signaling controlling transcytosis not delineated
    • Glycan recognition mechanism on receptor unclear
  19. 2017 Medium

    Confirmed in vivo that the FcγRIIB/SHIP1/PIP3 axis controls mast cell degranulation, mediating IVIG therapeutic benefit after hemorrhage.

    Evidence ICH mouse model with in vivo SHIP1 siRNA knockdown and degranulation/neurological readouts

    PMID:29138419

    Open questions at the time
    • Single lab
    • IgG species engaging FcγRIIB in vivo not defined
  20. 2018 High

    Provided a structural mechanism for the I232T polymorphism, showing TM tilt bends the ectodomain to reduce IgG binding affinity.

    Evidence Single-cell FRET, molecular dynamics, and in situ 2D binding kinetics

    PMID:31343409

    Open questions at the time
    • Link between altered affinity and disease risk in vivo not demonstrated here
  21. 2018 Medium

    Identified FcγRIIB as a neuronal α-synuclein fibril receptor driving prion-like transmission via SHP-1/SHP-2.

    Evidence Co-culture transmission assay with FcγRIIB blockade/KO and SHP-1/2 phosphorylation

    PMID:29298416

    Open questions at the time
    • Single lab
    • Direct fibril-receptor binding affinity not quantified
  22. 2019 High

    Demonstrated stage-dependent, opposing roles of FcγRIIB at pre- and post-immune B-cell tolerance checkpoints.

    Evidence Deficient and transgenic mice with defined autoreactive BCR models and germinal-center analysis

    PMID:31036800

    Open questions at the time
    • Molecular basis of opposing effects at the two checkpoints unresolved
  23. 2019 High

    Showed FcγRIIB on follicular dendritic cells shapes germinal-center B-cell selection and clonal diversity.

    Evidence Stromal-specific KO with confetti clonal tracking and mutation analysis

    PMID:31775042

    Open questions at the time
    • Signaling consequence of FDC FcγRIIB engagement not defined
  24. 2020 High

    Established a cell-intrinsic apoptotic pathway in CD8+ T cells, with Fgl2 triggering caspase-3/7 to limit T-cell accumulation independently of IgG.

    Evidence Cell-intrinsic Fcgr2b KO CD8+ T cells, Fgl2 binding, caspase assays, and IgG-deficient controls in graft/tumor models

    PMID:31940267

    Open questions at the time
    • Signaling between FcγRIIB and caspase activation in T cells not mapped
  25. 2022 High

    Separated an ITIM-independent competition mechanism, showing FcγRIIB blocks therapeutic antibody depletion by sequestering Fc from activating FcγRs.

    Evidence ITIM-null knock-in transgenic models with in vivo depletion and ADCP assays across CD20, CD25, OX40

    PMID:35858562

    Open questions at the time
    • Quantitative contribution of competition vs ITIM signaling in disease unclear
  26. 2022 High

    Identified marginal-zone B cells as a key cellular locus where high FcγRIIB restrains extrafollicular autoantibody responses.

    Evidence Conditional KO with Notch2 double-KO epistasis, signaling readouts, and human SLE validation

    PMID:35819855

    Open questions at the time
    • Why MZ B cells express the highest FcγRIIB not explained
  27. 2023 High

    Showed FcγRIIB on CD8+ T cells limits checkpoint-inhibitor responsiveness in a cell-intrinsic, Fc-dependent manner.

    Evidence Conditional Fcgr2b KO, Fc-devoid anti-PD-1 F(ab), multiple tumor models, and human melanoma patient analysis

    PMID:37611081

    Open questions at the time
    • Whether the Fc-dependent effect uses ITIM/SHIP or competition not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the divergent FcγRIIB outputs—SHIP-dependent inhibition, ITIM-independent Fc competition, FGL2-driven apoptosis, and neuronal aggregate sensing—are mechanistically unified or selected in different cell types remains unresolved.
  • No structural model linking ligand identity to choice of downstream effector
  • Switch between inhibitory and pro-apoptotic signaling undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0060089 molecular transducer activity 3 GO:0001618 virus receptor activity 2 GO:0038024 cargo receptor activity 1
Localization
GO:0005886 plasma membrane 4
Pathway
R-HSA-168256 Immune System 5 R-HSA-162582 Signal Transduction 4 R-HSA-5357801 Programmed Cell Death 2
Partners
CLEC7AFGL2MARCH3SHIP

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 SHP-1 is dispensable for FcγRIIB-mediated inhibition of B cell antigen receptor (sIgM) signaling; instead, SHIP (inositol 5'-phosphatase) is recruited to tyrosyl-phosphorylated FcγRIIB and mediates inhibition of calcium influx and CD19 dephosphorylation in B cells. Immortalized B cell lines from motheaten (SHP-1-deficient) mice and normal littermates; co-ligation of FcγRIIB and sIgM; calcium influx assays; co-immunoprecipitation of SHIP with FcγRIIB The Journal of biological chemistry High 9242674
1999 FcγRIIB co-ligation with the B cell antigen receptor suppresses Akt activation by reducing PIP3 accumulation via SHIP-mediated hydrolysis, despite normal PI3K activation; SHIP acts downstream of FcγRIIB to consume PIP3 and block Akt. A20 murine B cell line; sIg-FcγRIIB co-clustering; PIP3 measurement; Akt kinase assays; comparison with SHIP-deficient avian B cells and fibroblasts expressing catalytically active vs. inactive SHIP The Journal of biological chemistry High 10224144
2002 FcγRIIB negatively regulates mast cell proliferation when co-aggregated with Kit (SCF receptor): inhibits G1 entry, cyclins D2/D3/A induction, ERK/JNK/p38 activation, and Akt phosphorylation via SHIP recruitment; SHIP-null cells lose Akt and ERK inhibition but retain partial proliferation inhibition; a chimeric FcγRIIB bearing SHIP's catalytic domain mimics full inhibition. Mast cell co-aggregation assays; thymidine incorporation; cell cycle analysis; SHIP co-precipitation with FcγRIIB; SHIP-/- cells; chimeric receptor constructs Molecular immunology High 12217398
2002 A 13-nt deletion polymorphism in the Fcgr2b promoter found in autoimmune-prone NZB mice abolishes AP-4 transcription factor binding, reducing FcγRIIB1 expression in germinal center B cells and increasing IgG antibody responses. Luciferase reporter assays; EMSA and Southwestern analysis for AP-4 binding; congenic C57BL/6 mice carrying NZB Fcgr2b allele Journal of immunology High 12370366
2003 The I232T (Ile187Thr in earlier numbering) transmembrane domain polymorphism of FcγRIIB alters receptor signaling: the 187T allele mediates greater CD19 dephosphorylation and stronger inhibition of BCR-induced calcium response than 187I, independently of the ITIM, when co-engaged with BCR; both alleles similarly modulate BCR-induced and anti-Fas-induced apoptosis. Expression of both allelic forms (full-length and ITIM-truncated) in FcγRIIB-negative IIA1.6 mouse B cell line; CD19 phosphorylation assays; calcium flux assays; apoptosis assays Arthritis and rheumatism High 14613290
2004 A less-frequent FCGR2B promoter haplotype drives increased expression of FcγRIIB in luciferase reporter assays in both B lymphoid and myeloid cell lines under constitutive and stimulated conditions, and is associated with SLE susceptibility. Luciferase reporter assays; identification of 10 novel SNPs; case-control genetic study in 600 Caucasians Journal of immunology Medium 15153543
2005 FcγRIIB mediates CRP inhibition of endothelial NO synthase (eNOS): CRP signals through FcγRIIB expressed in endothelium to activate PP2A, blunting eNOS phosphorylation at Ser1179 and impairing vasodilatation in vivo. Cultured endothelium; siRNA knockdown of PP2A; heterologous FcγRIIB expression; FcγRIIB+/+ vs FcγRIIB-/- mice with acetylcholine vascular conductance assays; aggregated IgG as FcγR ligand Circulation research High 16269657
2007 FcγRIIB is expressed on bone marrow plasma cells; crosslinking FcγRIIB on plasma cells induces apoptosis, controlling their persistence in the bone marrow. Plasma cells from lupus-prone mice lack FcγRIIB expression and are protected from apoptosis. Human plasmablasts and FcγRIIB-expressing myeloma cells are also killed by FcγRIIB crosslinking. Flow cytometry of plasma cell FcγRIIB expression; crosslinking antibody-induced apoptosis assays; comparison between wild-type and lupus-prone mouse plasma cells; human plasmablast and myeloma cell assays Nature immunology High 17322888
2008 Cell-type-specific overexpression of FcγRIIB reveals distinct roles: B cell overexpression reduces IgG responses and ameliorates collagen-induced arthritis and SLE; macrophage overexpression has no effect on autoimmunity but increases mortality after S. pneumoniae infection. Transgenic mice overexpressing FcγRIIB under B cell- or macrophage-specific promoters; T-dependent immune response assays; collagen-induced arthritis model; S. pneumoniae infection model The Journal of experimental medicine High 18362174
2008 FGL2 (fibrinogen-like protein 2) binds specifically to FcγRIIB and FcγRIII on APC surfaces; FcγRIIB binding mediates FGL2-induced inhibition of DC maturation and apoptosis of FcγRIIB+ B cells; FcγRIIB is required for FGL2's immunosuppressive and allograft-prolonging effects in vivo. Flow cytometry and surface plasmon resonance for FGL2–FcγRIIB binding; FcγRIIB-/- vs wild-type BMDC maturation assays; A20 vs A20IIA1.6 (FcγRIIB-negative) apoptosis assay; skin allograft survival in FcγRIIB+/+ vs FcγRIIB-/- mice European journal of immunology High 18991288
2008 FcγRIIB co-aggregation with BCR dampens BCR-induced BLyS receptor upregulation in a SHIP1-dependent manner, subsequently attenuating BLyS survival signals (Pim-2, non-canonical NF-κB, Bcl-xL) in B cells. B cell co-aggregation assays; BLyS receptor expression and signaling assays; SHIP1-deficient cells; pharmacological dissection Blood Medium 18791164
2012 Galactosylated IgG1 immune complexes promote association of FcγRIIB with dectin-1, leading to SHIP phosphorylation downstream of FcγRIIB and Syk downstream of dectin-1, which blocks C5aR-mediated ERK1/2 phosphorylation and suppresses complement-mediated inflammatory responses in vitro and in vivo; high IgG N-glycan galactosylation is required for FcγRIIB–dectin-1 association. Co-immunoprecipitation of FcγRIIB with dectin-1; SHIP and Syk phosphorylation assays; ERK1/2 phosphorylation; peritonitis and epidermolysis bullosa acquisita mouse models; glycan-manipulated IgG1 Nature medicine High 22922409
2013 FcγRIIB expressed in neurons mediates Aβ oligomer neurotoxicity in Alzheimer's disease: soluble Aβ oligomers interact directly with neuronal FcγRIIB, activating ER stress and caspase-12; Fcgr2b KO neurons are resistant to Aβ-induced cell death, and Fcgr2b deficiency rescues LTP inhibition and memory impairment in an AD mouse model. In vitro binding assay (Aβ–FcγRIIB interaction); Fcgr2b KO primary neurons; caspase-12/ER stress assays; LTP recordings; memory behavioral tests in AD mouse model The Journal of clinical investigation High 23921129
2015 TLR4 activation of monocytes by LPS induces MARCH3 (E3 ubiquitin ligase) upregulation, leading to ubiquitination of FcγRIIB protein and its downregulation; siRNA knockdown of MARCH3 prevents LPS-induced FcγRIIB loss. TLR agonist screening; ubiquitination assay of FcγRIIB in LPS-treated monocytes; MARCH3 siRNA knockdown; microarray-identified MARCH3 upregulation The Journal of biological chemistry Medium 26694610
2015 FcγRIIB mediates anti-CD28 superagonist TGN1412 activity: FcγRIIB expression on monocytes (which is logarithmically upregulated during high-density preculture) is necessary and sufficient for TGN1412-mediated T cell proliferation, acting by crosslinking the antibody. High-density vs low-density preculture PBMC assays; FcγRIIB expression measurement by flow cytometry; reconstitution experiments mixing FcγRIIB+ monocytes with LD T cells; B cell FcγRIIB functional assay Blood Medium 25395427
2015 FcγRIIB mediates antigen-independent inhibition of human B cells (naïve B cells, memory B cells, and plasma cells) through Btk and p38 MAPK; FcγRIIB crosslinking eliminates antibody-secreting plasma cells and blocks naïve B cell proliferation without affecting memory B cell activation. FcγRIIB crosslinking on sorted human B cell subsets; Btk and p38 MAPK inhibitor assays; proliferation and differentiation assays Journal of biomedical science Medium 26475492
2017 FcγRIIB activation by hyposialylated IgG in endothelium impairs endothelial cell insulin transcytosis, reducing insulin delivery to skeletal muscle and causing obesity-induced insulin resistance; endothelium-specific FcγRIIB deletion protects mice from HFD-induced insulin resistance; IgG from T2DM patients is hyposialylated and causes insulin resistance via FcγRIIB. Global and endothelium-specific FcγRIIB KO mice; HFD model; IgG transfer into IgG-deficient mice; in vitro endothelial insulin transcytosis assay; IgG sialylation analysis The Journal of clinical investigation High 29202472
2017 IVIG attenuates post-ICH mast cell activation via the FcγRIIB/SHIP1/PIP3 pathway: FcγRIIB engagement activates SHIP1, hydrolyzing PIP3 and inhibiting calcium mobilization and mast cell degranulation; in vivo siRNA knockdown of SHIP1 abolishes IVIG's protective effects. ICH collagenase mouse model; siRNA-mediated in vivo SHIP1 knockdown; mast cell degranulation assays; brain edema and neurological function assessment Scientific reports Medium 29138419
2018 The I232T polymorphism in the transmembrane domain of FcγRIIB tilts the TM domain, bending the ectodomain toward the plasma membrane to allosterically impede ligand (IgG1/IgG2/IgG3) binding, reducing in situ 2D binding affinities and association rates by 3–4 fold. Single-cell FRET assay; molecular dynamics simulations; in situ 2D binding kinetics measurements eLife (PMID 31343409, published 2019) High 31343409
2018 FcγRIIB expressed in neurons acts as a receptor for α-synuclein fibrils and mediates cell-to-cell transmission (prion-like propagation) of α-syn; SHP-1 and SHP-2 are activated downstream of FcγRIIB by α-syn fibrils and are required for α-syn transmission and Lewy body-like inclusion formation. Co-culture neuronal transmission assay; FcγRIIB-blocking/KO experiments; SHP-1/SHP-2 phosphorylation assays; Lewy body-like inclusion quantification Cell reports Medium 29298416
2019 FcγRIIB differentially regulates B cell tolerance checkpoints: reduced FcγRIIB enhances deletion/anergy of autoreactive immature B cells (pre-immune checkpoint) but promotes autoreactive B cell expansion in germinal centers and autoantibody production (post-immune checkpoint), demonstrating opposing effects at distinct developmental stages. FcγRIIB-deficient and transgenic mice; B cell tolerance assays with defined autoreactive BCR models; germinal center analysis; autoantibody measurement Nature communications High 31036800
2019 Follicular dendritic cells (FDCs) upregulate FcγRIIB during germinal center (GC) formation; FDC-specific FcγRIIB deficiency leads to aberrant GC B cell selection, increased GC diversity (persistence of IgM+ clones, fewer IgH mutations), indicating FDCs modulate GC B cell selection via FcγRIIB. Stromal-specific FcγRIIB KO mice; AidCreERT2-confetti clonal tracking; GC B cell frequency and mutation analysis; autoreactive and foreign antigen immunization models Cell reports High 31775042
2020 FcγRIIB is expressed on a subset of effector CD8+ T cells following activation; cell-intrinsic FcγRIIB signaling induces caspase-3/7-mediated apoptosis in CD8+ T cells upon engagement by its functional ligand fibrinogen-like protein 2 (Fgl2), thereby limiting CD8+ T cell accumulation; IgG is not required for this pathway. Fcgr2b cell-intrinsic KO CD8+ T cells; graft rejection and tumor models; caspase-3/7 apoptosis assay; Fgl2 binding assay; IgG-deficient mouse controls Immunity High 31940267
2022 FcγRIIB inhibits antibody-mediated target cell depletion through competition with activating FcγRs for antibody Fc binding, independently of ITIM signaling; ITIM-null FcγRIIB expressed on target or effector cells still impairs mAb-mediated depletion through three therapeutically relevant surface receptors (CD20, CD25, OX40). Human FcγRIIB transgenic models with ITIM-intact vs ITIM-mutant receptors on targets or effectors; in vivo tumor depletion assays; in vitro ADCP assays Cell reports High 35858562
2022 FcγRIIB expression in marginal zone (MZ) B cells is highest among B cell subsets; high FcγRIIB expression limits MZ B cell activation, ERK phosphorylation, and calcium flux; B cell-conditional Fcgr2b KO leads to spontaneous IgG3 autoantibody increase driven by extrafollicular MZ B cell responses. Fcgr2b conditional KO mice; MZ B cell subset analysis by flow cytometry; ERK phosphorylation and calcium flux assays; Notch2/Fcgr2b double KO to eliminate MZ B cells The Journal of clinical investigation High 35819855
2023 FcγRIIB on CD8+ T cells limits responsiveness to PD-1 checkpoint inhibition in a cell-intrinsic, Fc-dependent manner: FcγRIIBpos CD8+ T cells show reduced response to PD-1 and CTLA-4 checkpoint inhibitors; conditional Fcgr2b deletion on tumor-specific CD8+ T cells improves checkpoint blockade response; Fc-devoid anti-PD-1 F(ab) restores FcγRIIBpos T cell proliferation. Conditional Fcgr2b KO on CD8+ T cells; Fc-devoid F(ab) anti-PD-1 comparison; in vivo B16, LLC, and MC38 tumor models; human melanoma patient FcγRIIBpos CD8+ T cell analysis Science translational medicine High 37611081
2016 CRP activates Smad3 via the CD32b–ERK/p38 MAP kinase crosstalk pathway (within 15 min, directly) and through TGF-β1 (at 24 h, indirectly); CRP also activates mTOR signaling via a Smad3-dependent mechanism (Smad3 physically binds mTOR); CD32b neutralizing antibody and Smad3 inhibitor abolish CRP-induced mTOR activation and renal fibrosis. CRPtg-db/db mouse model; in vitro renal tubular epithelial cell CRP stimulation; Smad3 inhibitor; CD32b neutralizing antibody; co-immunoprecipitation of Smad3 with mTOR; rapamycin treatment Scientific reports Medium 27221338

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 FcgammaRIIB in autoimmunity and infection: evolutionary and therapeutic implications. Nature reviews. Immunology 448 20414206
2012 Anti-inflammatory activity of IgG1 mediated by Fc galactosylation and association of FcγRIIB and dectin-1. Nature medicine 379 22922409
2002 Fcgamma receptor gene polymorphisms in Japanese patients with systemic lupus erythematosus: contribution of FCGR2B to genetic susceptibility. Arthritis and rheumatism 264 12115230
2007 FcgammaRIIb controls bone marrow plasma cell persistence and apoptosis. Nature immunology 236 17322888
2004 A promoter haplotype of the immunoreceptor tyrosine-based inhibitory motif-bearing FcgammaRIIb alters receptor expression and associates with autoimmunity. I. Regulatory FCGR2B polymorphisms and their association with systemic lupus erythematosus. Journal of immunology (Baltimore, Md. : 1950) 141 15153543
2003 A novel polymorphism in the Fcgamma receptor IIB (CD32B) transmembrane region alters receptor signaling. Arthritis and rheumatism 137 14613290
2009 Copy number variation at the FCGR locus includes FCGR3A, FCGR2C and FCGR3B but not FCGR2A and FCGR2B. Human mutation 131 19309690
2008 Distinct cell-specific control of autoimmunity and infection by FcgammaRIIb. The Journal of experimental medicine 127 18362174
2011 Antibody-mediated coengagement of FcγRIIb and B cell receptor complex suppresses humoral immunity in systemic lupus erythematosus. Journal of immunology (Baltimore, Md. : 1950) 119 21357255
2015 Antagonistic human FcγRIIB (CD32B) antibodies have anti-tumor activity and overcome resistance to antibody therapy in vivo. Cancer cell 116 25873171
2007 Monoclonal antibodies capable of discriminating the human inhibitory Fcgamma-receptor IIB (CD32B) from the activating Fcgamma-receptor IIA (CD32A): biochemical, biological and functional characterization. Immunology 115 17386079
2013 FcγRIIb mediates amyloid-β neurotoxicity and memory impairment in Alzheimer's disease. The Journal of clinical investigation 108 23921129
2020 Signaling through the Inhibitory Fc Receptor FcγRIIB Induces CD8+ T Cell Apoptosis to Limit T Cell Immunity. Immunity 96 31940267
2005 FcgammaRIIB mediates C-reactive protein inhibition of endothelial NO synthase. Circulation research 90 16269657
2008 The FGL2-FcgammaRIIB pathway: a novel mechanism leading to immunosuppression. European journal of immunology 89 18991288
2017 Hyposialylated IgG activates endothelial IgG receptor FcγRIIB to promote obesity-induced insulin resistance. The Journal of clinical investigation 86 29202472
2002 Transcriptional regulation of Fcgr2b gene by polymorphic promoter region and its contribution to humoral immune responses. Journal of immunology (Baltimore, Md. : 1950) 82 12370366
2017 Allergen-specific IgG antibody signaling through FcγRIIb promotes food tolerance. The Journal of allergy and clinical immunology 80 28479335
2009 IFN regulatory factor 5 is required for disease development in the FcgammaRIIB-/-Yaa and FcgammaRIIB-/- mouse models of systemic lupus erythematosus. Journal of immunology (Baltimore, Md. : 1950) 80 20007534
2010 FcgammaRIIB, FcgammaRIIIB, and systemic lupus erythematosus. Annals of the New York Academy of Sciences 79 20146709
2012 Reduction of total IgE by targeted coengagement of IgE B-cell receptor and FcγRIIb with Fc-engineered antibody. The Journal of allergy and clinical immunology 77 22257644
2013 Inhibitory FcγRIIb (CD32b) becomes activated by therapeutic mAb in both cis and trans and drives internalization according to antibody specificity. Blood 66 24227819
2006 CD32B, the human inhibitory Fc-gamma receptor IIB, as a target for monoclonal antibody therapy of B-cell lymphoma. Blood 66 16757681
2016 FcγRIIB and autoimmunity. Immunological reviews 65 26683154
2018 Prion-like Propagation of α-Synuclein Is Regulated by the FcγRIIB-SHP-1/2 Signaling Pathway in Neurons. Cell reports 60 29298416
2016 C-Reactive Protein Promotes Diabetic Kidney Disease in db/db Mice via the CD32b-Smad3-mTOR signaling Pathway. Scientific reports 60 27221338
2020 DPP4/CD32b/NF-κB Circuit: A Novel Druggable Target for Inhibiting CRP-Driven Diabetic Nephropathy. Molecular therapy : the journal of the American Society of Gene Therapy 57 32956626
2010 Therapeutic control of B cell activation via recruitment of Fcgamma receptor IIb (CD32B) inhibitory function with a novel bispecific antibody scaffold. Arthritis and rheumatism 55 20506263
2021 Acute Kidney Injury Induced Lupus Exacerbation Through the Enhanced Neutrophil Extracellular Traps (and Apoptosis) in Fcgr2b Deficient Lupus Mice With Renal Ischemia Reperfusion Injury. Frontiers in immunology 52 34248948
1997 Protein-tyrosine phosphatase SHP-1 is dispensable for FcgammaRIIB-mediated inhibition of B cell antigen receptor activation. The Journal of biological chemistry 52 9242674
2006 The functional variant of the inhibitory Fcgamma receptor IIb (CD32B) is associated with the rate of radiologic joint damage and dendritic cell function in rheumatoid arthritis. Arthritis and rheumatism 51 17133580
1999 FcgammaRIIb modulation of surface immunoglobulin-induced Akt activation in murine B cells. The Journal of biological chemistry 50 10224144
2014 Upregulation of FcγRIIb on monocytes is necessary to promote the superagonist activity of TGN1412. Blood 49 25395427
2013 Cutting edge: Expression of FcγRIIB tempers memory CD8 T cell function in vivo. Journal of immunology (Baltimore, Md. : 1950) 49 24285839
2019 The Complex Association of FcγRIIb With Autoimmune Susceptibility. Frontiers in immunology 48 31681256
2008 FcgammaRIIB deficiency leads to autoimmunity and a defective response to apoptosis in Mrl-MpJ mice. Journal of immunology (Baltimore, Md. : 1950) 48 18390752
2014 CD19 and CD32b differentially regulate human B cell responsiveness. Journal of immunology (Baltimore, Md. : 1950) 46 24442430
2010 FcgammaRIIB inhibits the development of atherosclerosis in low-density lipoprotein receptor-deficient mice. Journal of immunology (Baltimore, Md. : 1950) 46 20097865
2019 Targeting the Antibody Checkpoints to Enhance Cancer Immunotherapy-Focus on FcγRIIB. Frontiers in immunology 42 30930905
2005 Hydronephrosis associated with antiurothelial and antinuclear autoantibodies in BALB/c-Fcgr2b-/-Pdcd1-/- mice. The Journal of experimental medicine 41 16352741
2017 A novel bispecific DARPin targeting FcγRIIB and FcεRI-bound IgE inhibits allergic responses. Allergy 40 27997998
2007 High synovial expression of the inhibitory FcgammaRIIb in rheumatoid arthritis. Arthritis research & therapy 38 17521421
2020 Syk Inhibitor Attenuates Polymicrobial Sepsis in FcgRIIb-Deficient Lupus Mouse Model, the Impact of Lupus Characteristics in Sepsis. Journal of innate immunity 37 32927460
2019 Lipocalin-2 (Lcn-2) Attenuates Polymicrobial Sepsis with LPS Preconditioning (LPS Tolerance) in FcGRIIb Deficient Lupus Mice. Cells 36 31514375
2007 Expression of the autoimmune Fcgr2b NZW allele fails to be upregulated in germinal center B cells and is associated with increased IgG production. Genes and immunity 36 17713556
2021 A Synergy Between Endotoxin and (1→3)-Beta-D-Glucan Enhanced Neutrophil Extracellular Traps in Candida Administered Dextran Sulfate Solution Induced Colitis in FcGRIIB-/- Lupus Mice, an Impact of Intestinal Fungi in Lupus. Journal of inflammation research 35 34103965
2019 Follicular Dendritic Cells Modulate Germinal Center B Cell Diversity through FcγRIIB. Cell reports 35 31775042
2008 CD32B is highly expressed on clonal plasma cells from patients with systemic light-chain amyloidosis and provides a target for monoclonal antibody-based therapy. Blood 35 18216299
2020 Dysregulation of Lipid Metabolism in Macrophages Is Responsible for Severe Endotoxin Tolerance in FcgRIIB-Deficient Lupus Mice. Frontiers in immunology 34 32582149
2017 Upregulation of FcγRIIB by resveratrol via NF-κB activation reduces B-cell numbers and ameliorates lupus. Experimental & molecular medicine 33 28960214
2001 Deregulation of FCGR2B expression by 1q21 rearrangements in follicular lymphomas. Oncogene 33 11753646
2021 Prominent Indomethacin-Induced Enteropathy in Fcgriib Defi-cient lupus Mice: An Impact of Macrophage Responses and Immune Deposition in Gut. International journal of molecular sciences 32 33573095
2020 Syk inhibitor attenuates inflammation in lupus mice from FcgRIIb deficiency but not in pristane induction: the influence of lupus pathogenesis on the therapeutic effect. Lupus 32 32700597
2012 Development and characterisation of monoclonal antibodies specific for the murine inhibitory FcγRIIB (CD32B). European journal of immunology 32 22760702
2003 FcgammaRIIB gene polymorphisms in Japanese periodontitis patients. Genes and immunity 32 14647193
2024 FcγRIIB Is an Immune Checkpoint Limiting the Activity of Treg-Targeting Antibodies in the Tumor Microenvironment. Cancer immunology research 31 38147316
2018 Tissue-Specific Expression of the Low-Affinity IgG Receptor, FcγRIIb, on Human Mast Cells. Frontiers in immunology 31 29928276
2018 New revelations from an old receptor: Immunoregulatory functions of the inhibitory Fc gamma receptor, FcγRIIB (CD32B). Journal of leukocyte biology 30 29406570
2008 FcgammaRIIB signals inhibit BLyS signaling and BCR-mediated BLyS receptor up-regulation. Blood 30 18791164
2002 Negative regulation of mast cell proliferation by FcgammaRIIB. Molecular immunology 30 12217398
2022 HIF activation enhances FcγRIIb expression on mononuclear phagocytes impeding tumor targeting antibody immunotherapy. Journal of experimental & clinical cancer research : CR 29 35392965
2019 IGFBP2 promotes immunosuppression associated with its mesenchymal induction and FcγRIIB phosphorylation in glioblastoma. PloS one 29 31560714
2014 Regulation of IgE-mediated signalling in human basophils by CD32b and its role in Syk down-regulation: basic mechanisms in allergic disease. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 29 24734927
2013 Immunotherapy targeting inhibitory Fcγ receptor IIB (CD32b) in the mouse is limited by monoclonal antibody consumption and receptor internalization. Journal of immunology (Baltimore, Md. : 1950) 29 24026082
2021 FcγRIIB is a T cell checkpoint in antitumor immunity. JCI insight 27 33616086
2007 FcgammaRIIB regulates autoreactive primary antibody-forming cell, but not germinal center B cell, activity. Journal of immunology (Baltimore, Md. : 1950) 27 17202351
2019 Decreased Protein Kinase C-β Type II Associated with the Prominent Endotoxin Exhaustion in the Macrophage of FcGRIIb-/- Lupus Prone Mice is Revealed by Phosphoproteomic Analysis. International journal of molecular sciences 26 30889825
2019 FcγRIIb differentially regulates pre-immune and germinal center B cell tolerance in mouse and human. Nature communications 26 31036800
2014 FcγRIIB as a key determinant of agonistic antibody efficacy. Current topics in microbiology and immunology 26 25116108
2009 FCGR2B gene polymorphism rather than FCGR2A, FCGR3A and FCGR3B is associated with anti-GBM disease in Chinese. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 26 19640933
2013 FCGR2B and FCRLB gene polymorphisms associated with IgA nephropathy. PloS one 25 23593433
2012 FcγRIIB: a modulator of cell activation and humoral tolerance. Expert review of clinical immunology 25 22390489
2012 FcγRIIb and BAFF differentially regulate peritoneal B1 cell survival. Journal of immunology (Baltimore, Md. : 1950) 25 22516957
2022 FcγRIIB regulates autoantibody responses by limiting marginal zone B cell activation. The Journal of clinical investigation 24 35819855
2017 IVIG activates FcγRIIB-SHIP1-PIP3 Pathway to stabilize mast cells and suppress inflammation after ICH in mice. Scientific reports 24 29138419
2019 FcγRIIB-I232T polymorphic change allosterically suppresses ligand binding. eLife 23 31343409
2018 Transmembrane domain dependent inhibitory function of FcγRIIB. Protein & cell 23 29497990
2015 FcγRIIB mediates antigen-independent inhibition on human B lymphocytes through Btk and p38 MAPK. Journal of biomedical science 23 26475492
2022 FcγRIIB controls antibody-mediated target cell depletion by ITIM-independent mechanisms. Cell reports 22 35858562
2010 FcγRIIB regulation of BCR/TLR-dependent autoreactive B-cell responses. European journal of immunology 21 20809520
2004 Intravenous immunoglobulin does not increase FcgammaRIIB expression on monocytes/macrophages during acute Kawasaki disease. Rheumatology (Oxford, England) 21 15572393
2023 C-reactive protein impairs immune response of CD8+ T cells via FcγRIIb-p38MAPK-ROS axis in multiple myeloma. Journal for immunotherapy of cancer 20 37844994
2014 FcγRIIB regulates T-cell autoreactivity, ANCA production, and neutrophil activation to suppress anti-myeloperoxidase glomerulonephritis. Kidney international 20 24869670
2011 Immune complex enhances tolerogenecity of immature dendritic cells via FcγRIIb and promotes FcγRIIb-overexpressing dendritic cells to attenuate lupus. European journal of immunology 20 21360699
2023 FcγRIIB expressed on CD8+ T cells limits responsiveness to PD-1 checkpoint inhibition in cancer. Science translational medicine 19 37611081
2021 Lipopolysaccharide-Enhanced Responses against Aryl Hydrocarbon Receptor in FcgRIIb-Deficient Macrophages, a Profound Impact of an Environmental Toxin on a Lupus-Like Mouse Model. International journal of molecular sciences 19 33919603
2020 FcγRIIB engagement drives agonistic activity of Fc-engineered αOX40 antibody to stimulate human tumor-infiltrating T cells. Journal for immunotherapy of cancer 19 32900860
2015 Toll-like Receptor 4 Ligands Down-regulate Fcγ Receptor IIb (FcγRIIb) via MARCH3 Protein-mediated Ubiquitination. The Journal of biological chemistry 19 26694610
2014 IgG receptor FcγRIIB plays a key role in obesity-induced hypertension. Hypertension (Dallas, Tex. : 1979) 19 25368023
2012 Low expression of FCGRIIB in macrophages of immune thrombocytopenia-affected individuals. International journal of hematology 19 23054650
2004 FcgammaRIIB is differentially expressed during B cell maturation and in B-cell lymphomas. British journal of haematology 19 14675408
2022 Antibody-Targeted TNFRSF Activation for Cancer Immunotherapy: The Role of FcγRIIB Cross-Linking. Frontiers in pharmacology 18 35865955
2024 Clec12A, CD301b, and FcγRIIB/III define the heterogeneity of murine DC2s and DC3s. Cell reports 17 38492222
2023 The CD16 and CD32b Fc-gamma receptors regulate antibody-mediated responses in mouse natural killer cells. Journal of leukocyte biology 17 36822164
2009 Selective regulation of autoreactive B cells by FcgammaRIIB. Journal of autoimmunity 17 19327966
2020 Memory T cell-mediated rejection is mitigated by FcγRIIB expression on CD8+ T cells. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 16 32154641
2018 Increased susceptibility against Cryptococcus neoformans of lupus mouse models (pristane-induction and FcGRIIb deficiency) is associated with activated macrophage, regardless of genetic background. Journal of microbiology (Seoul, Korea) 16 30456753
2016 Immunohistochemical detection of CD14 and combined assessment with CD32B and CD68 for wound age estimation. Forensic science international 16 26974714
2013 CD40 mediates downregulation of CD32B on specific memory B cell populations in rheumatoid arthritis. Journal of immunology (Baltimore, Md. : 1950) 16 23686494
2012 Increased incidence of anti-GBM disease in Fcgamma receptor 2b deficient mice, but not mice with conditional deletion of Fcgr2b on either B cells or myeloid cells alone. Molecular immunology 16 22244885

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