Affinage

CD37

Leukocyte antigen CD37 · UniProt P11049

Length
281 aa
Mass
31.7 kDa
Annotated
2026-04-28
89 papers in source corpus 25 papers cited in narrative 25 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD37 is a tetraspanin that organizes membrane signaling complexes on leukocytes, coupling receptor compartmentalization to intracellular signal transduction, integrin function, cytoskeletal dynamics, and metabolic control. Upon ligation, CD37 undergoes tyrosine phosphorylation at N-terminal ITIM-like and C-terminal ITAM motifs, recruiting SHP1 to initiate apoptotic signaling or PI3K to promote survival, respectively (PMID:22624718, PMID:40675974). CD37 restrains IL-6 signaling through interaction with SOCS3, thereby suppressing germinal center–derived B-cell lymphomagenesis and preventing IgA nephropathy; genetic ablation of IL-6 fully rescues both pathologies in CD37-deficient mice (PMID:26784544, PMID:29551516, PMID:19282981). CD37 also organizes integrins (α4β1, α4β7, αIIbβ3, β2), the BCR complex, dectin-1, CLEC-2, CD20, and FATP1 at the cell surface, regulating integrin-dependent adhesion and Akt survival signaling, Rac-1-dependent dendritic cell and neutrophil migration, BCR endocytosis and MHC class II antigen presentation, platelet activation, and fatty acid uptake (PMID:23150881, PMID:40250439, PMID:40126944, PMID:26566675, PMID:30185523, PMID:38625120, PMID:36100608).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1989 High

    Establishing CD37 as a tetraspanin resolved the fundamental question of its membrane topology, revealing four transmembrane domains with short cytoplasmic tails and an extracellular loop bearing N-linked glycosylation sites.

    Evidence cDNA cloning and primary sequence analysis of the 244-amino acid protein

    PMID:2466944

    Open questions at the time
    • No information on post-translational modifications beyond glycosylation
    • Functional role of the short cytoplasmic domains unknown
  2. 1994 High

    Demonstrating that CD37 co-precipitates with MHC class II, CD19, and other tetraspanins established that it participates in large multicomponent membrane complexes on B cells, raising the question of its organizing function.

    Evidence Co-immunoprecipitation and preclearing experiments from B-cell lines and tonsillar B cells

    PMID:8119731

    Open questions at the time
    • Whether CD37 directly contacts MHC II or interacts indirectly through tetraspanin networks
    • Functional consequence of complex formation unknown
  3. 2000 High

    The first CD37 knockout mice revealed impaired T-cell-dependent IgG1 responses, establishing a non-redundant role for CD37 in humoral immunity and T–B cell cooperation.

    Evidence Cd37−/− mice immunized with T-dependent antigens with and without adjuvant, serum Ig quantification

    PMID:10891477

    Open questions at the time
    • Molecular mechanism by which CD37 supports T–B interaction undefined
    • Whether the defect is B-cell- or T-cell-intrinsic unresolved
  4. 2004 High

    Showing that CD37 deficiency causes T-cell hyperproliferation with enhanced Lck kinase activity, and that CD37 cross-linking inhibits TCR-driven proliferation, revealed CD37 as a negative regulator of proximal TCR signaling.

    Evidence Cd37−/− T-cell proliferation assays, Lck activity measurement, CD37 cross-linking on human T cells

    PMID:14978098

    Open questions at the time
    • Direct physical connection between CD37 and the TCR/Lck complex not shown
    • Mechanism of Lck suppression unknown
  5. 2007 High

    Identification of dectin-1 as a CD37 partner on APCs, where CD37 stabilizes dectin-1 surface expression and restrains dectin-1-induced IL-6 production, provided the first evidence that CD37 negatively controls innate immune cytokine output.

    Evidence Co-localization, Cd37−/− macrophage cytokine assays, rescue by CD37 transfection

    PMID:17182550

    Open questions at the time
    • Mechanism of dectin-1 internalization control by CD37 not defined
    • Whether CD37-dectin-1 interaction is direct or within tetraspanin web unclear
  6. 2009 High

    Demonstrating that CD37 loss causes 15-fold elevated IgA via B-cell-intrinsic IL-6 overproduction—reversible by IL-6 neutralization—identified the CD37/IL-6 axis as a master regulator of IgA class switching, linking CD37 to IgA nephropathy pathogenesis.

    Evidence Cd37−/− mice, bone marrow chimeras, IL-6 neutralization in vivo, serum IgA quantification

    PMID:19282981

    Open questions at the time
    • How CD37 restrains IL-6 at the molecular level not yet identified
    • Relevance to human IgA nephropathy not directly tested
  7. 2012 High

    Mapping ITIM-like (N-terminal Tyr → SHP1 → apoptosis) and ITAM (C-terminal Tyr → PI3K → survival) motifs on CD37 established it as a direct signal transducer, not merely a membrane organizer, resolving a long-standing question about tetraspanin signaling competence.

    Evidence Site-directed mutagenesis of tyrosine residues, SHP1 Co-IP, PI3K pathway analysis, apoptosis assays

    PMID:22624718

    Open questions at the time
    • Identity of the kinase(s) that phosphorylate CD37 tyrosines unknown
    • Whether both motifs are simultaneously active in the same cell context unclear
  8. 2012 High

    Showing that CD37 controls α4β1 integrin clustering and VCAM-1-dependent Akt activation in plasma cells linked the tetraspanin membrane-organizing function to integrin-mediated survival signaling in germinal centers.

    Evidence Cd37−/− mice, integrin clustering imaging, Akt phosphorylation, VCAM-1 binding assays

    PMID:23150881

    Open questions at the time
    • Whether CD37 directly binds α4β1 or acts through lateral tetraspanin interactions not resolved
    • Structural basis of integrin clustering by CD37 unknown
  9. 2013 High

    Demonstrating that CD37 is required for DC migration from skin to lymph nodes, chemotaxis, and integrin-mediated adhesion under flow established CD37 as essential for cellular immunity beyond humoral responses.

    Evidence Cd37−/− mice, intravital multiphoton imaging, in vitro chemotaxis and flow chamber assays

    PMID:23420539

    Open questions at the time
    • Specific integrin(s) organized by CD37 during DC migration not identified
    • Downstream cytoskeletal effector undefined at this stage
  10. 2015 High

    Identifying dysregulated Rac-1 activation and accelerated β2 integrin internalization in CD37-deficient neutrophils established a cytoskeletal mechanism—Rac-1-dependent actin polymerization—for CD37's role in leukocyte adhesion and migration.

    Evidence Cd37−/− neutrophils, peritonitis model, intravital microscopy, superresolution microscopy, Rac-1 activation assays

    PMID:26566675

    Open questions at the time
    • How CD37 activates Rac-1 (direct or via GEF recruitment) unknown
    • Superresolution showed CD37 and CD18 do not co-cluster, so the spatial mechanism of action remains unclear
  11. 2016 High

    Identification of SOCS3 as a CD37 interaction partner, combined with genetic epistasis showing that IL-6 deletion rescues CD37−/− lymphomagenesis, established CD37 as a tumor suppressor acting through SOCS3-dependent restraint of constitutive IL-6 signaling.

    Evidence Co-IP (CD37–SOCS3), Cd37−/− lymphoma model, Cd37/Il6 double-knockout rescue

    PMID:26784544

    Open questions at the time
    • Whether CD37 stabilizes SOCS3 protein levels or recruits it to IL-6 receptor complexes not distinguished
    • Applicability to human DLBCL treatment not functionally tested
  12. 2018 High

    Genetic epistasis confirmed that IL-6 is the causative mediator of IgA nephropathy in CD37-deficient mice, as Cd37/Il6 double knockouts were fully protected from glomerular IgA deposition and renal failure.

    Evidence Cd37/Il6 double-knockout mice, renal histopathology, IgA and IL-6 quantification

    PMID:29551516

    Open questions at the time
    • Translational relevance to human IgA nephropathy not validated
    • Whether therapeutic IL-6 blockade recapitulates the protective effect untested
  13. 2018 High

    Showing that CD37 directly interacts with CLEC-2 and is required for CLEC-2-dependent DC migration and actin protrusion formation upon podoplanin stimulation extended CD37's organizing function to C-type lectin receptor–mediated migration.

    Evidence Co-IP (CLEC-2/CD37), Cd37−/− DC migration in 3D collagen matrices, microcontact printing

    PMID:30185523

    Open questions at the time
    • Whether CD37 controls CLEC-2 signaling beyond surface stabilization unknown
    • Role in lymph node architecture in vivo not fully characterized
  14. 2022 High

    Discovery that CD37 directly binds FATP1 and inhibits fatty acid uptake and oxidation in B-cell lymphoma expanded CD37's functional repertoire to metabolic regulation, with FATP1 inhibition reversing the metabolic phenotype of CD37-deficient cells.

    Evidence Co-IP (CD37–FATP1), FA oxidation assays, metabolomics, FATP1 inhibitor rescue, in vivo mouse studies

    PMID:36100608

    Open questions at the time
    • Structural basis of CD37–FATP1 interaction unknown
    • Whether metabolic control contributes to CD37's tumor suppressor function independently of IL-6 pathway not established
  15. 2022 High

    Identifying IRF8 as a direct transcriptional activator of CD37 via promoter binding addressed the upstream regulation of CD37 expression, providing a mechanistic basis for CD37 loss in DLBCL lacking IRF8.

    Evidence DNA pulldown/mass spectrometry, ChIP, IRF8 overexpression, CRISPR/Cas9 IRF8 knockout in DLBCL

    PMID:35086136

    Open questions at the time
    • Other transcription factors regulating CD37 not explored
    • Whether IRF8 loss explains CD37 downregulation across all lymphoma subtypes unknown
  16. 2023 High

    Mutagenesis of N-glycosylation sites showed glycosylation is required for CD37 surface expression and modulates partner interactions (CD53, CD20) in a localization-dependent manner, while IL-6Rα interaction is glycosylation-independent.

    Evidence Glycosylation mutants, flow cytometry, single-molecule dSTORM super-resolution microscopy, Co-IP

    PMID:38031400

    Open questions at the time
    • Which specific glycan structures are functionally important not defined
    • Impact of glycosylation on CD37 signaling through ITIM/ITAM motifs not tested
  17. 2024 High

    Demonstrating that CD20 forms a complex with CD37 and stabilizes its surface expression—with CD20 knockout causing CD37 downregulation and increased internalization—revealed reciprocal stabilization within the tetraspanin network relevant to antibody therapy.

    Evidence CD20 KO cell lines, Co-IP (CD20/CD37), internalization assays, CDC assays

    PMID:38846084

    Open questions at the time
    • Whether CD37 reciprocally stabilizes CD20 not tested
    • Implications for sequential anti-CD20/anti-CD37 therapy not clinically validated
  18. 2024 High

    Proximity proteomics identified CD37 as a BCR-proximal protein; CD37 knockout heightened BCR signaling, slowed BCR endocytosis, and reduced pMHC-II formation, establishing CD37 as a modulator of antigen processing via BCR dynamics.

    Evidence BioID proximity labeling + mass spectrometry, CRISPR CD37 KO, BCR signaling and endocytosis assays, MHC II antigen presentation assay

    PMID:38625120

    Open questions at the time
    • Direct physical contact between CD37 and specific BCR subunits not confirmed by reciprocal IP
    • Whether CD37's effect on BCR is through lateral membrane organization or direct binding not resolved
  19. 2025 High

    Extension of CD37's integrin-organizing function to platelets (αIIbβ3) and AML leukemic stem cells (α4β7/PI3K-AKT) demonstrated tissue-broad roles in integrin signaling, thrombosis regulation, and leukemia maintenance.

    Evidence Cd37−/− platelet assays, FeCl3 carotid thrombosis model, bone marrow chimeras; Co-IP (CD37/α4β7), AML serial transplantation in Cd37 KO mice

    PMID:40126944 PMID:40250439

    Open questions at the time
    • Structural interface between CD37 and different integrins not characterized
    • Whether CD37-integrin interactions are direct or mediated by other tetraspanins not resolved for all integrin partners
  20. 2025 High

    Identification of tumor-derived MIF as an extrinsic CD37 ligand that triggers Y13 phosphorylation, SHP1 recruitment, and AKT inhibition in macrophages revealed a tumor immune evasion mechanism operating through CD37's ITIM-like motif.

    Evidence Direct MIF-CD37 binding assays, Y13 phosphorylation identification, SHP1/AKT signaling, in vitro phagocytosis and in vivo tumor models

    PMID:40675974

    Open questions at the time
    • Whether MIF binding to CD37 occurs in physiological non-tumor contexts unknown
    • Crystal structure of MIF-CD37 interaction not available

Open questions

Synthesis pass · forward-looking unresolved questions
  • The identity of the kinase(s) phosphorylating CD37 ITIM-like and ITAM tyrosines, the structural basis of CD37–integrin and CD37–FATP1 interactions, and whether CD37's metabolic and IL-6-restraining tumor suppressor functions operate independently or synergistically remain unresolved.
  • No kinase identified for CD37 tyrosine phosphorylation
  • No atomic-resolution structure of CD37 or its complexes
  • Relative contribution of metabolic vs. IL-6 pathway control to tumor suppression not dissected

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 6 GO:0098772 molecular function regulator activity 3 GO:0060089 molecular transducer activity 2
Localization
GO:0005886 plasma membrane 5 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-168256 Immune System 8 R-HSA-162582 Signal Transduction 5 R-HSA-5357801 Programmed Cell Death 2 R-HSA-109582 Hemostasis 1 R-HSA-1430728 Metabolism 1
Partners
CD20CLEC2FATP1ITGA4ITGB1MIFSHP1SOCS3
Complex memberships
CD20-CD37 complexTetraspanin-enriched microdomain (TEM)

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1988 CD37 (gp40-52) is a single-chain protein with ~25 kDa core bearing two N-linked complex carbohydrate chains (comprising ~50% of total molecular mass); it localizes both at the cell surface and in association with intracellular vesicles, as determined by biochemical fractionation and electron microscopy. Biochemical analysis (glycosidase digestion, SDS-PAGE), electron microscopy, subcellular fractionation Journal of immunology High 3257508
1989 CD37 is a 244-amino acid protein lacking a conventional leader sequence, with an N-terminal cytoplasmic domain followed by four transmembrane segments (three in the first 110 residues) and a hydrophilic region containing three N-linked glycosylation sites, establishing it as a four-transmembrane-spanning (tetraspanin) protein. cDNA cloning and primary sequence analysis The Journal of experimental medicine High 2466944
1994 CD37, CD53, TAPA-1, and R2/C33 tetraspanins co-precipitate with MHC class II (DR) antigens along with CD19 and CD21 from mild detergent lysates of B cells, forming large multicomponent membrane complexes. Co-immunoprecipitation and preclearing experiments from B-cell line and tonsillar B-cell lysates Immunogenetics High 8119731
2000 CD37-deficient mice show impaired T-cell-dependent IgG1 antibody responses to antigens administered without adjuvant and to viral infections, demonstrating that CD37 is required for optimal T-cell–B-cell interactions under suboptimal costimulatory conditions. Targeted gene knockout (CD37-/- mice), humoral immune response assays, serum immunoglobulin quantification Molecular and cellular biology High 10891477
2004 CD37 negatively regulates T-cell proliferation by dampening early TCR signaling; CD37-deficient T cells are hyperproliferative with enhanced early IL-2 production, and CD4/CD8-associated p56(Lck) kinase activity is increased in CD37-/- T cells. Cross-linking of CD37 on human T cells completely inhibits CD3-induced proliferation. CD37-/- mouse T-cell proliferation assays, IL-2 measurement, p56(Lck) kinase activity assay, CD37 cross-linking experiments Journal of immunology High 14978098
2007 CD37 interacts with the C-type lectin pattern-recognition receptor dectin-1 on APC membranes; CD37 stabilizes dectin-1 at the cell surface by inhibiting its internalization, and CD37 deficiency causes a 10-fold increase in dectin-1-induced IL-6 production despite reduced surface dectin-1. Co-localization studies, CD37-/- macrophage analysis, CD37 transfection into macrophage cell line, cytokine measurement Journal of immunology High 17182550
2009 CD37 inhibits IgA immune responses in vivo; CD37-/- mice show 15-fold elevated serum IgA and increased IgA+ plasma cells. Bone marrow chimera experiments showed B-cell-intrinsic CD37 deficiency drives increased IgA production. CD37 deficiency leads to high local IL-6 in germinal centers, and neutralizing IL-6 in vivo reverses the elevated IgA response. CD37-/- mice, bone marrow chimeras, serum IgA quantification, IL-6 neutralization in vivo, flow cytometry PLoS pathogens High 19282981
2009 CD37 and CD151 differentially regulate dendritic cell function: CD37 controls peptide/MHC class II antigen presentation while CD151 regulates co-stimulation, as shown by hyper-stimulatory phenotypes in CD37-/- and CD151-/- DCs toward antigen-specific T cells. DC-T cell co-stimulation assays using CD37-/- and CD151-/- DCs, antigen presentation assays European journal of immunology High 19089816
2012 Upon ligation, CD37 becomes tyrosine phosphorylated and associates with proximal signaling molecules. An N-terminal ITIM-like motif (Tyr) mediates SHP1-dependent apoptotic signaling, while a C-terminal ITAM motif (Tyr) counteracts death signals via PI3K-dependent survival signaling, demonstrating CD37 directly transduces both death and survival signals. Site-directed mutagenesis of tyrosine residues, phosphoprotein assays, SHP1 co-immunoprecipitation, PI3K pathway analysis, apoptosis assays Cancer cell High 22624718
2012 CD37 is essential for α4β1 integrin-mediated Akt survival signaling in IgG-secreting plasma cells; CD37 regulates the mobility and clustering of α4β1 integrins in the plasma membrane, and CD37-/- plasma cells show impaired VCAM-1/α4β1-dependent Akt activation and increased apoptosis in germinal centers. CD37-/- mice, plasma cell survival assays, integrin clustering by imaging, Akt phosphorylation assays, VCAM-1 binding experiments Science signaling High 23150881
2013 CD37 promotes dendritic cell migration from skin to draining lymph nodes, chemotactic migration, integrin-mediated adhesion under flow, cell spreading and actin protrusion formation. CD37-/- mice fail to induce antigen-specific IFN-γ-secreting T cells after intradermal challenge, demonstrating CD37 is required for cellular immunity via DC migration. CD37-/- mouse in vivo tumor challenge, intravital multiphoton microscopy of DC migration, in vitro chemotaxis assays, flow chamber adhesion assays European journal of immunology High 23420539
2015 CD37 regulates β2 integrin-mediated neutrophil adhesion and recruitment; CD37-/- neutrophils show impaired ICAM-1 adhesion, reduced actin polymerization, impaired cell spreading and polarization, dysregulated Rac-1 activation, and accelerated β2 integrin internalization. Superresolution microscopy showed CD37 and CD18 do not significantly co-cluster, suggesting CD37 acts downstream of integrin-mediated adhesion via cytoskeletal regulation. CD37-/- mice, peritonitis model, intravital microscopy, flow chamber adhesion assays, superresolution microscopy, Rac-1 activation assays, actin polymerization assays Journal of immunology High 26566675
2016 CD37 interacts with SOCS3 (suppressor of cytokine signaling 3); loss of CD37 drives constitutive activation of the IL-6 signaling pathway, leading to germinal center-derived B-cell lymphoma development. Double knockout of Cd37 and Il6 fully protected mice from lymphoma, placing CD37 as a tumor suppressor acting via SOCS3-dependent inhibition of IL-6 signaling. Co-immunoprecipitation (CD37-SOCS3 interaction), CD37-/- mouse lymphoma model, Cd37/Il6 double-knockout mice, lymphoma incidence analysis The Journal of clinical investigation High 26784544
2016 CD37 and CD82 have opposing roles in coordinating dendritic cell migration and antigen presentation; CD37 promotes Rac-1 activation and cell migration (CD37-/- BMDCs spread poorly on fibronectin), while CD82 is a negative regulator of RhoA. Both tetraspanins negatively regulate Cdc42. An unactivated DC is CD37(hi)CD82(lo) (highly motile, limited T-cell activation capacity), while a late-activated DC is CD37(lo)CD82(hi) (adapted for T-cell activation). CD37-/- and CD82-/- BMDC functional assays, small GTPase activation assays (Rac-1, RhoA, Cdc42), fibronectin spreading assays, T-cell stimulation assays Journal of immunology High 26729805
2018 CLEC-2-dependent dendritic cell migration is controlled by CD37; CD37 specifically interacts with CLEC-2, and CD37-deficient DCs express reduced surface CLEC-2. Cd37-/- DCs show impaired adhesion, migration velocity and displacement on lymph node stromal cells, failure to form actin protrusions upon podoplanin-induced CLEC-2 stimulation, and CD37 is required for CLEC-2 recruitment to its ligand podoplanin in the membrane. Co-immunoprecipitation (CLEC-2/CD37 interaction), CD37-/- DC migration assays, 3D collagen matrix assays, microcontact printing, surface CLEC-2 quantification Journal of cell science High 30185523
2018 IL-6 is essential for glomerular IgA deposition and renal pathology in CD37-deficient mice; Cd37/Il6 double-knockout mice are fully protected from glomerular IgA deposition and accelerated renal failure, establishing CD37 inhibition of the IL-6 pathway as the mechanism protecting against IgA nephropathy. Cd37-/-, Il6-/-, and Cd37xIl6 double-knockout mice, renal histopathology, IgA quantification, IL-6 serum measurement Kidney international High 29551516
2022 CD37 inhibits fatty acid (FA) metabolism in B-cell lymphoma by directly interacting with the fatty acid transporter FATP1; deletion of CD37 increases FA oxidation and uptake of exogenous palmitate. Inhibition of FATP1 reverses the metabolic phenotype of CD37-deficient lymphoma cells. Functional FA oxidation assays, metabolomics, co-immunoprecipitation (CD37-FATP1), FATP1 inhibition experiments, in vivo mouse studies, patient tissue analysis Nature communications High 36100608
2022 IRF8 is a transcriptional activator of CD37 gene expression in DLBCL; IRF8 directly binds the CD37 promoter region (confirmed by DNA pulldown/mass spectrometry and ChIP), and IRF8 overexpression enhances CD37 protein levels while CRISPR/Cas9 knockout of IRF8 decreases CD37 expression. Quantitative nuclear proteomics, DNA pulldown + mass spectrometry, ChIP, IRF8 overexpression, CRISPR/Cas9 IRF8 knockout, immunohistochemistry Blood advances High 35086136
2023 N-glycosylation of CD37 is required for its surface expression; abrogation of CD37 glycosylation reduces surface CD37 levels. CD37 interaction with partner proteins CD53 and CD20 is affected by glycosylation in a localization-dependent manner, while its interaction with IL-6Rα is glycosylation-independent. Glycosylation mutant generation, flow cytometry, single-molecule dSTORM super-resolution microscopy, co-immunoprecipitation Biophysical journal High 38031400
2024 CD20 and CD37 form a complex in the B-cell membrane; CD20 stabilizes CD37 at the cell surface. CD20 knockout results in downregulation of CD37, increased internalization of anti-CD37 mAb, and reduced complement-dependent cytotoxicity that can be partially restored by lysosome inhibition. CD20 knockout cell lines, co-immunoprecipitation (CD20/CD37 complex), flow cytometry, internalization assays, CDC assays Oncoimmunology High 38846084
2024 CD37 is a BCR-proximal protein; CRISPR-based knockout of CD37 in a B-cell line heightens BCR signaling, slows BCR endocytosis, and tempers formation of peptide-MHC class II complexes, demonstrating CD37 modulates membrane-mediated BCR functions. Proximity-based biotinylation (BioID) + mass spectrometry, CRISPR/Cas9 CD37 knockout, BCR signaling assays, BCR endocytosis assays, MHC class II antigen presentation assay ImmunoHorizons High 38625120
2025 CD37 interacts with integrin α4β7 and activates the PI3K-AKT pathway mediated by integrin signaling in AML leukemic stem cells; CD37 deficiency impairs LSC self-renewal, colony formation, and leukemia maintenance in vivo without affecting normal hematopoiesis. Co-immunoprecipitation (CD37/integrin α4β7), CD37 knockdown/KO in AML cell lines and mouse models, AKT phosphorylation assays, serial transplantation assays Stem cell reports High 40250439
2025 Tumor-derived macrophage migration inhibitory factor (MIF) directly binds to CD37, promoting phosphorylation of CD37 at Y13, recruiting SHP1, and inhibiting AKT signaling, thereby impairing macrophage phagocytosis. Targeting CD37 with an antibody promotes phagocytosis of multiple cancer cell types. Direct binding assays (MIF-CD37), phosphorylation site identification (CD37 Y13), SHP1 recruitment assay, AKT signaling assay, in vitro phagocytosis assays, in vivo tumor clearance models Nature communications High 40675974
2025 DuoHexaBody-CD37 (biparatopic anti-CD37 antibody) induces significant CD37 clustering at the cell surface (without internalization), upregulates p-SHP1(Y564) in DLBCL cells (while primary B cells show increased p-AKT and MAPK survival signaling), and inhibits cytokine pro-survival signaling in DLBCL. The CD37 N-terminus is required for DuoHexaBody-CD37-induced signaling. CD37 clustering imaging, phosphoproteomic screen (26 phosphoproteins), CD37 N-terminus mutants, SHP1/AKT/MAPK pathway analysis bioRxivpreprint Medium bio_10.1101_2025.02.24.639899
2025 CD37 positively regulates platelet activation and thrombosis; Cd37-/- platelets exhibit impaired integrin αIIbβ3 signaling (reduced fibrinogen spreading and decreased agonist-induced αIIbβ3 activation), and Cd37-/- bone marrow chimeric mice show significantly increased time to vessel occlusion in a carotid artery FeCl3 thrombosis model. Cd37-/- mice, bone marrow chimera thrombosis model (carotid FeCl3), platelet αIIbβ3 activation assays, fibrinogen spreading assays, RNA-sequencing Cardiovascular research High 40126944

Source papers

Stage 0 corpus · 89 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1994 Association of four antigens of the tetraspans family (CD37, CD53, TAPA-1, and R2/C33) with MHC class II glycoproteins. Immunogenetics 165 8119731
1992 Imaging, dosimetry, and radioimmunotherapy with iodine 131-labeled anti-CD37 antibody in B-cell lymphoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 139 1403053
2018 Anti-CD37 chimeric antigen receptor T cells are active against B- and T-cell lymphomas. Blood 117 30089630
1992 C33 antigen recognized by monoclonal antibodies inhibitory to human T cell leukemia virus type 1-induced syncytium formation is a member of a new family of transmembrane proteins including CD9, CD37, CD53, and CD63. Journal of immunology (Baltimore, Md. : 1950) 115 1401919
2012 Tetraspanin CD37 directly mediates transduction of survival and apoptotic signals. Cancer cell 113 22624718
2007 Targeting CD37-positive lymphoid malignancies with a novel engineered small modular immunopharmaceutical. Blood 112 17440052
2004 A regulatory role for CD37 in T cell proliferation. Journal of immunology (Baltimore, Md. : 1950) 104 14978098
1989 The primary structure of the human leukocyte antigen CD37, a species homologue of the rat MRC OX-44 antigen. The Journal of experimental medicine 103 2466944
1988 The B cell-associated CD37 antigen (gp40-52). Structure and subcellular expression of an extensively glycosylated glycoprotein. Journal of immunology (Baltimore, Md. : 1950) 101 3257508
2000 Targeted inactivation of the tetraspanin CD37 impairs T-cell-dependent B-cell response under suboptimal costimulatory conditions. Molecular and cellular biology 97 10891477
2012 The tetraspanin CD37 orchestrates the α(4)β(1) integrin-Akt signaling axis and supports long-lived plasma cell survival. Science signaling 86 23150881
2011 A novel Fc-engineered monoclonal antibody to CD37 with enhanced ADCC and high proapoptotic activity for treatment of B-cell malignancies. Blood 84 21795744
2007 Dectin-1 interaction with tetraspanin CD37 inhibits IL-6 production. Journal of immunology (Baltimore, Md. : 1950) 83 17182550
2015 AGS67E, an Anti-CD37 Monomethyl Auristatin E Antibody-Drug Conjugate as a Potential Therapeutic for B/T-Cell Malignancies and AML: A New Role for CD37 in AML. Molecular cancer therapeutics 78 25934707
2013 A novel anti-CD37 antibody-drug conjugate with multiple anti-tumor mechanisms for the treatment of B-cell malignancies. Blood 74 24002446
2016 Assessment of CD37 B-cell antigen and cell of origin significantly improves risk prediction in diffuse large B-cell lymphoma. Blood 73 27760757
1990 The human leucocyte surface antigen CD53 is a protein structurally similar to the CD37 and MRC OX-44 antigens. Immunogenetics 73 1700763
2009 Tetraspanins CD37 and CD151 differentially regulate Ag presentation and T-cell co-stimulation by DC. European journal of immunology 64 19089816
2013 A phase 1 study evaluating the safety and tolerability of otlertuzumab, an anti-CD37 mono-specific ADAPTIR therapeutic protein in chronic lymphocytic leukemia. Blood 60 24381226
2020 DuoHexaBody-CD37®, a novel biparatopic CD37 antibody with enhanced Fc-mediated hexamerization as a potential therapy for B-cell malignancies. Blood cancer journal 57 32341336
2009 The tetraspanin protein CD37 regulates IgA responses and anti-fungal immunity. PLoS pathogens 56 19282981
2019 CD20 and CD37 antibodies synergize to activate complement by Fc-mediated clustering. Haematologica 50 30792198
2016 Tetraspanin CD37 protects against the development of B cell lymphoma. The Journal of clinical investigation 49 26784544
2013 Tetraspanin CD37 contributes to the initiation of cellular immunity by promoting dendritic cell migration. European journal of immunology 48 23420539
2009 TRU-016, a humanized anti-CD37 IgG fusion protein for the potential treatment of B-cell malignancies. Current opinion in investigational drugs (London, England : 2000) 44 19943209
2016 Dendritic Cell Migration and Antigen Presentation Are Coordinated by the Opposing Functions of the Tetraspanins CD82 and CD37. Journal of immunology (Baltimore, Md. : 1950) 41 26729805
2013 Targeted drug delivery and cross-linking induced apoptosis with anti-CD37 based dual-ligand immunoliposomes in B chronic lymphocytic leukemia cells. Biomaterials 40 23726226
1993 Delivery of saporin to human B-cell lymphoma using bispecific antibody: targeting via CD22 but not CD19, CD37, or immunoglobulin results in efficient killing. Cancer research 40 7686448
2018 Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study. Investigational new drugs 39 29453628
2010 A complementary role for the tetraspanins CD37 and Tssc6 in cellular immunity. Journal of immunology (Baltimore, Md. : 1950) 39 20709950
1997 Expression of tetra-spans transmembrane family (CD9, CD37, CD53, CD63, CD81 and CD82) in normal and neoplastic human keratinocytes: an association of CD9 with alpha 3 beta 1 integrin. The British journal of dermatology 39 9470900
2014 Otlertuzumab (TRU-016), an anti-CD37 monospecific ADAPTIR(™) therapeutic protein, for relapsed or refractory NHL patients. British journal of haematology 37 25146490
2013 Evaluating antigen targeting and anti-tumor activity of a new anti-CD37 radioimmunoconjugate against non-Hodgkin's lymphoma. Anticancer research 36 23267131
1987 Use of the monoclonal antibody WR17, identifying the CD37 gp40-45 Kd antigen complex, in the diagnosis of B-lymphoid malignancy. The Journal of pathology 36 3305845
2018 Interleukin-6 is essential for glomerular immunoglobulin A deposition and the development of renal pathology in Cd37-deficient mice. Kidney international 33 29551516
2015 Tetraspanin CD37 Regulates β2 Integrin-Mediated Adhesion and Migration in Neutrophils. Journal of immunology (Baltimore, Md. : 1950) 32 26566675
2020 Targeted alpha therapy for chronic lymphocytic leukaemia and non-Hodgkin's lymphoma with the anti-CD37 radioimmunoconjugate 212Pb-NNV003. PloS one 31 32187209
2022 Fatty acid metabolism in aggressive B-cell lymphoma is inhibited by tetraspanin CD37. Nature communications 30 36100608
2017 The Antitumor Activity of IMGN529, a CD37-Targeting Antibody-Drug Conjugate, Is Potentiated by Rituximab in Non-Hodgkin Lymphoma Models. Neoplasia (New York, N.Y.) 30 28753442
2014 The CD37-targeted antibody-drug conjugate IMGN529 is highly active against human CLL and in a novel CD37 transgenic murine leukemia model. Leukemia 29 24445867
2020 CD37 in B Cell Derived Tumors-More than Just a Docking Point for Monoclonal Antibodies. International journal of molecular sciences 26 33333768
1994 Leukemia-associated changes identified by quantitative flow cytometry. III. B-cell gating in CD37/kappa/lambda clonality test. Leukemia 24 7967732
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