Affinage

CD72

B-cell differentiation antigen CD72 · UniProt P21854

Length
359 aa
Mass
40.2 kDa
Annotated
2026-06-09
100 papers in source corpus 32 papers cited in narrative 30 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 10/10 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD72 is a type II transmembrane C-type lectin-like receptor that serves as a tunable inhibitory co-receptor governing B cell development and activation (PMID:2645579, PMID:10549631). Its founding topology places the C-type lectin-like domain extracellularly with an inverted membrane orientation lacking an N-terminal signal peptide, defining it within a receptor superfamily including the asialoglycoprotein receptor and CD23 (PMID:2645579). The cytoplasmic tail carries two ITIMs: tyrosine-phosphorylated ITIM1 recruits the phosphatase SHP-1 to deliver a strong negative signal, while ITIM2 recruits Grb2 (and an associated BLNK-containing complex) that moderates the SHP-1 signal (PMID:9590210, PMID:9740800, PMID:10820378, PMID:15816000). BCR cross-linking drives CD72 tyrosine phosphorylation and SHP-1 association, and CD72 is itself an in vivo SHP-1 substrate whose phosphorylation correlates with BCR-induced growth arrest and apoptosis (PMID:9590210, PMID:9740800). Through this ITIM/SHP-1 axis CD72 dampens BCR-induced ERK and Ca²⁺ mobilization, with downstream suppression of NF-AT, NF-κB, MAPK and PI3K/Akt signaling; an intact ITIM is required for inhibition (PMID:10640734, PMID:16621999). Genetic loss of CD72 in mice perturbs B cell development and produces hyperproliferative, Ca²⁺-hyperresponsive B cells, and in antigen-specific anergic settings CD72-deficient B cells inappropriately survive and aged mice develop lupus-like autoimmunity, the latter linked to physical association with and regulation of Cbl-b (PMID:10549631, PMID:18821699). The receptor's extracellular CTLD recognizes the RNA-containing lupus self-antigen Sm/RNP to specifically restrain TLR7-driven B cell responses; the hypofunctional CD72c allele shows altered charge at the ligand-binding site, weaker Sm/RNP binding, and acts as a modifier of lupus susceptibility (PMID:27810925, PMID:23616572). CD72 binding partners include CD5 on T cells and the semaphorin CD100/Sema4D, whose engagement induces CD72 dephosphorylation and SHP-1 dissociation to switch off inhibitory signaling and set BCR signal sensitivity (PMID:1711157, PMID:1371783, PMID:11114375, PMID:12882840, PMID:16113236). Beyond its inhibitory role, CD72 ligation can deliver positive, Syk-independent signals by activating Lyn, Blk and Btk and recruiting CD19-associated PI3-kinase (PMID:9531290, PMID:9808169). CD72 functions analogously as an inhibitory receptor on NK cells and mast cells (PMID:20100931, PMID:19197938).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1987 Medium

    Established that engaging CD72 (Lyb-2) triggers an intrinsic signaling response, distinct from cytokine pathways, indicating it is not merely a passive surface marker.

    Evidence Anti-Lyb-2 antibody-induced phosphatidylinositol hydrolysis assay in murine B cells with BSF-1 competition controls

    PMID:3499987

    Open questions at the time
    • No molecular identity of the signaling intermediates
    • Allele specificity unexplained at the structural level
  2. 1989 High

    Defined the molecular architecture of CD72, resolving that it is an inverted type II C-type lectin-like receptor rather than a conventional receptor.

    Evidence cDNA sequencing and predicted topology analysis placing it in a C-type lectin superfamily with the asialoglycoprotein receptor and CD23

    PMID:2645579

    Open questions at the time
    • No ligand identified at this stage
    • No functional consequence of the lectin fold tested
  3. 1991 High

    Identified the first CD72 binding partner, CD5 on T cells, establishing CD72 as a mediator of T-B cell communication.

    Evidence Biotin-labeled CD5 probe binding, antibody blocking, and gain-of-function CD72 transfection into non-B cells

    PMID:1371783 PMID:1711157

    Open questions at the time
    • Downstream signaling consequence of CD5-CD72 binding not defined
    • Affinity and stoichiometry not quantified
  4. 1998 High

    Resolved the proximal signaling machinery, showing CD72's cytoplasmic ITIM recruits SHP-1 upon BCR-induced phosphorylation and that CD72 is an in vivo SHP-1 substrate whose phosphorylation tracks with growth arrest/apoptosis; also mapped both positive (Lyn/Blk/Btk, CD19-PI3K) and negative arms.

    Evidence ITIM phosphopeptide pull-down, co-IP from BCR-stimulated B cells, kinase activity assays, xid (Btk-deficient) B cells, and reciprocal CD19/CD72 co-IP

    PMID:9531290 PMID:9590210 PMID:9740800 PMID:9808169

    Open questions at the time
    • How a single receptor switches between positive and negative outputs unresolved
    • CD19-CD72 association is transient and from a single lab (#7)
  5. 1998 High

    Identified the transcriptional basis of B-cell-restricted CD72 expression, linking lineage-specific gene control to PU.1.

    Evidence DNase I footprinting, EMSA, and reporter mutagenesis of the PU.1 site in B vs non-B cells

    PMID:9498769

    Open questions at the time
    • Other regulatory inputs to CD72 expression not mapped
    • No link between expression level and signaling output
  6. 1999 High

    Demonstrated through genetics that CD72 is a nonredundant negative regulator of B cell activation and development in vivo, not merely an in vitro signaling artifact.

    Evidence CD72-knockout mice with B cell subset flow cytometry, proliferation, and intracellular Ca²⁺ measurements

    PMID:10549631

    Open questions at the time
    • Did not connect phenotype to a physiological ligand
    • Developmental versus activation roles not mechanistically separated
  7. 2000 High

    Identified CD100/Sema4D as the physiological ligand and defined the regulatory logic: CD100 binding dephosphorylates CD72 and dissociates SHP-1, switching off inhibition; ITIM mutagenesis confirmed the ITIM is required for negative signaling; BLNK was placed in the CD72/SHP-1/Grb2 complex.

    Evidence Expression cloning, affinity measurement, dephosphorylation and SHP-1 dissociation assays, ITIM-mutant transfection with ERK/Ca²⁺ readouts, and quaternary complex co-IP

    PMID:10640734 PMID:10820378 PMID:11114375

    Open questions at the time
    • BLNK complex shown by single-lab co-IP (#8)
    • How CD100 engagement mechanistically drives CD72 dephosphorylation not resolved
  8. 2005 High

    Dissected the two ITIMs functionally and established CD100 sets BCR signal sensitivity in vivo, with CD100 loss causing constitutive SHP-1 association, hyporesponsiveness, and aging autoimmunity.

    Evidence ITIM Tyr-to-Phe mutant panels with growth-inhibition readout and CD100-knockout mice with CD72-BCR co-IP and autoantibody measurement

    PMID:15816000 PMID:16113236

    Open questions at the time
    • ITIM2/Grb2 moderation mechanism (#10) from single lab
    • Structural basis of constitutive CD72-BCR association unknown
  9. 2008 High

    Connected CD72 directly to tolerance and autoimmunity, showing it enforces anergy by limiting antigen-induced signaling and by regulating Cbl-b, with its loss producing lupus-like disease.

    Evidence CD72-knockout HEL-BCR transgenic mice, Ca²⁺/NF-κB/NFAT/MAPK/Akt assays, and Cbl-b co-IP

    PMID:18821699

    Open questions at the time
    • Mechanism by which CD72 regulates Cbl-b not detailed
    • Did not identify the self-antigen recognized
  10. 2013 High

    Established the CD72c allele as a hypofunctional lupus modifier gene through genetic epistasis, linking allelic variation in CD72 to autoimmune disease severity.

    Evidence Congenic mouse strains with allele swaps and BCR signaling comparison plus disease scoring

    PMID:23616572

    Open questions at the time
    • Structural/biochemical basis of CD72c hypofunction not yet defined at this step
    • Human relevance of the murine allele not addressed
  11. 2016 High

    Provided the structural and mechanistic explanation for CD72's autoimmune specificity, showing the extracellular CTLD directly binds Sm/RNP to suppress TLR7-driven responses and that CD72c bears charge alterations weakening this binding.

    Evidence CTLD-Sm/RNP binding assay, TLR7-dependent B cell inhibition assay, and X-ray crystallography of the CD72c CTLD

    PMID:27810925

    Open questions at the time
    • Co-crystal structure of CTLD with Sm/RNP not solved
    • How CTLD ligand recognition couples to cytoplasmic ITIM signaling unresolved
  12. 2014 Medium

    Extended CD72 inhibitory function beyond B cells to NK cells and mast cells, revealing both shared (SHP-1) and species-divergent (Cbl-b) effector usage.

    Evidence Ectopic CD72 expression with IFN-γ readout in NK line, and CD72 ligation in human and mouse mast cells with SHP-1/Cbl-b co-IP and functional assays

    PMID:19197938 PMID:20100931 PMID:25239131

    Open questions at the time
    • Mechanistic basis of human/mouse mast cell divergence unexplained
    • NK and mast cell findings each from single labs
  13. 2025 Medium

    Identified new ligands and a soluble form of CD72 acting on T cells, indicating CD72 functions beyond a membrane-bound B cell receptor.

    Evidence Sema3A co-IP and signaling in SLE B cells; soluble CD72 binding CD100 and CD6 on T cells with phenotypic and pathway readouts in sepsis and inflammation models

    PMID:36470209 PMID:39026665 PMID:39793226

    Open questions at the time
    • Soluble CD72 mechanism (cytoplasmic entry, CD6/CD100 engagement) from single labs
    • Physiological source and abundance of soluble CD72 not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How extracellular CTLD ligand recognition (Sm/RNP, CD100, CD5, Sema3A) is structurally transmitted to the dual-ITIM cytoplasmic module to bias positive versus negative signaling remains unresolved.
  • No structure of CD72 ectodomain bound to any ligand
  • No reconstituted model coupling ligand binding to ITIM phosphorylation state
  • Determinants selecting SHP-1 inhibition versus Lyn/Btk/CD19-PI3K activation 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:0060090 molecular adaptor activity 3 GO:0001618 virus receptor activity 2
Localization
GO:0005886 plasma membrane 2 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 4 R-HSA-1643685 Disease 3
Partners
BLNKBTKCBL-BCD100CD19CD5GRB2SHP-1

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 CD72 (Lyb-2) on B cells is the ligand for CD5 on T cells. Purified biotinylated CD5 protein specifically bound CD72-expressing cells; binding was blocked by anti-CD72 antibodies; non-B cells (mouse L-cell fibroblasts and human Jurkat T cells) transfected with human CD72 cDNA acquired the ability to bind CD5-biotin conjugate. Biotin-labeled CD5 probe binding assay, antibody blocking, transfection of CD72 cDNA into non-B cells Nature High 1371783 1711157
2000 CD72 is the receptor for the class IV semaphorin CD100/Sema4D on lymphocytes (Kd ≈ 3×10⁻⁷ M). CD100 stimulation induces tyrosine dephosphorylation of CD72 and dissociation of SHP-1 from CD72, thereby switching off CD72-mediated negative signaling in B cells. Expression cloning, binding affinity measurements, tyrosine phosphorylation assay, co-immunoprecipitation of SHP-1 from CD72 Immunity High 11114375 12882840 16113236
1998 The cytoplasmic domain of CD72 carries an ITIM that, upon tyrosine phosphorylation, recruits the tyrosine phosphatase SHP-1. BCR cross-linking enhances tyrosine phosphorylation of CD72 and its association with SHP-1 in B-cell line WEHI-231. In vitro ITIM phosphopeptide pull-down, co-immunoprecipitation from BCR-stimulated B cells Journal of Immunology High 9590210 9740800
1998 CD72 is an in vivo substrate of SHP-1 in B cells. Tyrosine phosphorylation of CD72 strongly correlates with BCR-induced growth arrest/apoptosis. The binding sites for SHP-1 and the adaptor Grb2 on CD72 were defined. Preligation of CD72 attenuated BCR-induced growth arrest/death signals in B cells. Co-immunoprecipitation from primary B cells and B-cell lines, correlation of CD72 phosphorylation with apoptosis, CD72 preligation rescue assay Current Biology High 9740800
1999 CD72-deficient mice show: (1) reduced mature recirculating B cells and accumulation of pre-B cells in bone marrow; (2) fewer mature B-2 cells and more B-1 cells in periphery; (3) hyperproliferative B cells and enhanced Ca²⁺ response following IgM cross-linking. CD72 is thus a nonredundant regulator of B cell development and a negative regulator of B cell activation. Gene knockout mouse model, flow cytometry of B cell subsets, proliferation assays, intracellular Ca²⁺ measurement Immunity High 10549631
2000 CD72 negatively regulates BCR signaling through its ITIM motif. Expression of CD72 in B lymphoma K46 cells down-modulates BCR-induced ERK activation and Ca²⁺ mobilization; this inhibition requires the intact ITIM, as an ITIM-mutated CD72 did not reduce ERK activation. Co-ligation of CD72 with BCR in normal spleen B cells also reduced BCR-mediated ERK activation. Transfection of wild-type vs. ITIM-mutant CD72, ERK activation assay, Ca²⁺ mobilization assay, co-ligation experiments in primary B cells Journal of Immunology High 10640734
1998 CD72 ligation activates Src-family kinases Lyn and Blk, and the Tec-family kinase Btk, but not Syk. Btk is required for CD72-induced B cell proliferation, as B cells from xid (Btk-deficient) mice are unresponsive to CD72-induced proliferation. CD72-mediated PLC-γ2 tyrosine phosphorylation occurs independently of Syk activation. Kinase activity assays after CD72 ligation, xid (Btk-deficient) mouse B cells, PLC-γ2 phosphorylation assay Journal of Immunology High 9531290
1998 CD72 ligation recruits CD19 and activates CD19-associated PI 3-kinase. CD72 ligation induces CD19 tyrosine phosphorylation and a transient physical association between CD19 and CD72. PI 3-K inhibitors block CD72-stimulated B cell proliferation. CD72 signaling is Syk-independent even when co-cross-linked with CD19. PI 3-K inhibitor assays, CD19 phosphorylation, co-immunoprecipitation of CD72 and CD19 European Journal of Immunology Medium 9808169
2000 The adaptor protein BLNK is associated with the CD72/SHP-1/Grb2 complex via the SH3 domain(s) of Grb2 in WEHI-231 cells after mIgM engagement, forming a CD72/SHP-1/Grb2/BLNK complex. Co-immunoprecipitation from BCR-stimulated WEHI-231 cells European Journal of Immunology Medium 10820378
2001 CD72 ligation induces ERK and JNK (but not p38) MAPK activation via PKC-dependent pathways, and CD72 signaling compensates for defective BCR signaling in Btk-deficient (xid) B cells, partially restoring proliferation to anti-IgM. This establishes CD72 as capable of inducing BCR-independent positive signaling. MAPK activation assays, PKC inhibitors, xid mouse B cells, proliferation assays Journal of Immunology Medium 11466342
2005 CD72 ITIM1 (which binds SHP-1) delivers a strong negative signal that is attenuated by ITIM2 (which binds Grb2). ITIM1-only mutants (Y7/F) showed the least sensitivity to growth inhibition, double ITIM mutants (Y7,39/F) were also less sensitive, and Y39/F (ITIM2 mutant) cells were unrecoverable, suggesting ITIM2/Grb2 acts as a moderator of ITIM1/SHP-1 negative signaling. ITIM tyrosine-to-phenylalanine mutagenesis in retroviral vectors, BCR cross-linking growth inhibition assay European Journal of Immunology High 15816000
2005 CD100 regulates BCR signal sensitivity by preventing constitutive association of CD72 with the BCR. In CD100-deficient mice, BCR signals are suppressed due to constitutive SHP-1 association with CD72, causing B-cell hyporesponsiveness and, with aging, accumulation of marginal zone B cells, elevated autoantibodies, and autoimmunity. CD100-knockout mice, BCR co-immunoprecipitation with CD72, B-cell functional assays, flow cytometry, autoantibody measurement International Immunology High 16113236
2008 In anergic B cells, CD72 down-regulates BCR signaling by limiting antigen-induced Ca²⁺ elevation and activation of NFATc1, NF-κB, MAPK, and Akt. CD72 is physically associated with and regulates the molecular adaptor Cbl-b in anergic B cells. CD72-deficient anergic B cells inappropriately proliferate and survive in response to self antigen, and aged CD72-deficient mice develop lupus-like autoimmune disease. CD72-knockout mice crossed with HEL-specific BCR transgenic mice, Ca²⁺ flux measurements, NF-κB/NFAT/MAPK/Akt signaling assays, co-immunoprecipitation of Cbl-b Arthritis and Rheumatism High 18821699
2016 CD72 binds the RNA-containing lupus self-antigen Sm/RNP through its extracellular C-type lectin-like domain (CTLD) and specifically inhibits B cell responses to Sm/RNP. X-ray crystallographic analysis of the lupus-susceptible CD72c allele CTLD reveals considerable alteration in charge at the putative ligand-binding site, which correlates with weaker Sm/RNP binding by CD72c compared with the lupus-resistant CD72a allele. CTLD-Sm/RNP binding assay, TLR7-dependent B cell response inhibition assay, x-ray crystallography of CD72c CTLD Journal of Experimental Medicine High 27810925
1989 CD72 (Lyb-2) is a type II transmembrane protein with inverted membrane orientation (C-terminus extracellular), lacking an N-terminal signal peptide, and is homologous to the asialoglycoprotein receptor and CD23, defining a gene superfamily of C-type lectin-like receptors with inverted orientation. cDNA sequencing, sequence comparison, predicted protein topology analysis Proceedings of the National Academy of Sciences USA High 2645579
2010 CD72 is expressed on human mast cells. Ligation of CD72 (by agonistic antibody or recombinant CD100) induces CD72 tyrosine phosphorylation and increased association with SHP-1, resulting in inhibition of KIT-induced Src family kinase and ERK1/2 phosphorylation. This reduces KIT-mediated mast cell proliferation, chemotaxis, and chemokine production. Flow cytometry for CD72 expression, co-immunoprecipitation of SHP-1 with CD72, phosphorylation assays, proliferation and chemotaxis assays Journal of Immunology High 20100931
2009 CD72 is expressed on mouse NK cells and inhibits IFN-γ production but not cytotoxicity. Ectopic expression of CD72 in the NK-cell line KY2 inhibits cytokine-induced IFN-γ production; this inhibitory effect is diminished by mutations in the intracellular inhibitory motifs or replacement of the extracellular domain. Ectopic CD72 expression in NK cell line, IFN-γ production assay, intracellular domain mutants, cytotoxicity assay European Journal of Immunology Medium 19197938
1998 PU.1/Spi-1 binds the CD72 promoter (footprint FP I) and is essential for B cell-specific promoter activity. Mutation of the PU.1 binding site abolishes B cell-specific CD72 promoter activity in transient reporter assays. DNase I footprinting, EMSA, reporter gene deletion and mutation analysis in B cells vs. non-B cells Journal of Immunology High 9498769
2006 CD72 loss-of-function in mature B lymphocytes (CD72-deficient HEL BCR transgenic mice) down-regulates BCR-induced NF-AT, NF-κB, ERK, JNK, p38-MAPK, and PI3K/Akt signaling pathways. CD72 ligation (mimicking CD100 binding) augments Ca²⁺ flux, IκBα activation, and ERK activity upon antigen stimulation, and CD72 promotes cell cycle arrest and apoptosis after antigen stimulation. CD72-knockout BCR-transgenic mice, luciferase reporter assays for NF-AT/NF-κB, MAPK/PI3K-Akt signaling assays, Ca²⁺ flux measurement, cell cycle and apoptosis analysis Journal of Immunology High 16621999
2004 CD72 loss-of-function in B cells (CD72-deficient BAL-17 cells) impairs BCR-mediated phosphorylation of CD19, Btk, Vav, and PLC-γ2, and CD19-PI3K association. Ca²⁺ release from intracellular stores is intact but extracellular Ca²⁺ influx is severely impaired. BCR-evoked ERK and JNK activation and growth inhibition are also blocked; these effects are reversed by re-expression of CD72. CD72-deficient B-cell lines generated from BAL-17 cells, phosphorylation assays, Ca²⁺ influx measurement, re-expression rescue experiment International Immunology High 15148289
2005 CD72 cross-linking in human naive B cells suppresses differentiation into plasma cells by down-regulating X-box binding protein 1 (XBP-1) and CD27 expression, without affecting PRDI-BF1. This inhibition is dependent on the stimulation context (SAC+IL-2 but not CD40 signaling or CpG). CD72 cross-linking, XBP-1 and PRDI-BF1 expression analysis, Ig synthesis measurement, CD27 flow cytometry European Journal of Immunology Medium 16047337
1987 Ligation of Lyb-2 (CD72) via monoclonal antibody induces phosphatidylinositol (PI) hydrolysis in murine B cells in a dose-dependent, allele-specific manner. This PI response is distinct from that induced by BSF-1 (IL-4), which does not induce a PI response and does not competitively inhibit anti-Lyb-2-induced PI turnover, indicating CD72 uses a different signaling pathway from BSF-1. PI metabolism assay in B cells, dose-response and allele-specificity controls, BSF-1 competition assay Cellular Immunology Medium 3499987
2004 CD72 stimulation of immature B cells (WEHIdelta) prevents BCR-induced apoptosis by sustaining c-Myc expression, inhibiting p27(Kip1) accumulation, and preventing NF-κB suppression after mIgM cross-linking. CD72 pre-ligation followed by mIgM cross-linking, c-Myc protein expression, p27(Kip1) level measurement, NF-κB activity assay Microbiology and Immunology Medium 14734859
2022 Semaphorin3A (Sema3A) binds CD72 on B cells as a novel ligand, independent of neuropilin-1. Sema3A binding induces CD72 tyrosine phosphorylation and association of CD72 with SHP-1 and SHP-2. This inhibits STAT-4 and HDAC-1 phosphorylation and induces p38-MAPK and PKC-theta phosphorylation in B cells. Co-immunoprecipitation of Sema3A-CD72 interaction, phosphorylation assays (CD72 tyrosine, SHP-1/2, STAT-4, HDAC-1, p38-MAPK, PKC-theta), neuropilin-1 independence validation, primary B cells from SLE patients Journal of Autoimmunity Medium 36470209
2012 The alternatively spliced human CD72 isoform lacking exon 8 (CD72Δex8) accumulates in the endoplasmic reticulum and fails to reach the cell surface and fails to regulate BCR signaling, whereas full-length CD72 (CD72fl) is efficiently transported to the cell surface and inhibits BCR signaling. Transfection of CD72fl and CD72Δex8 into mouse cell lines, subcellular fractionation/localization, BCR signaling inhibition assay BMC Immunology Medium 23268649
2013 CD72 ligation in the AML cell line Kasumi-1 (expressing mutant KIT) suppresses proliferation and enhances cell death (caspase-3 cleavage), associated with CD72 phosphorylation, CD72-SHP-1 complex formation, and dephosphorylation of Src family kinases and JNK. CD72 ligation with agonistic antibody and recombinant CD100, proliferation assay, caspase-3 cleavage, co-immunoprecipitation of SHP-1, Src and JNK phosphorylation assays Scientific Reports Medium 24713856
2014 In mouse mast cells, CD72 ligation inhibits KIT-mediated growth, IL-6 production, and chemotaxis via Cbl-b phosphorylation and downregulation of KIT and FcεRIα surface expression. Unlike human mast cells, CD72 in mouse mast cells does not signal through SHP-1 for these effects. IgE-triggered degranulation is also suppressed by CD72 ligation in mouse (but not human) mast cells. CD72 ligation in mouse bone marrow-derived mast cells, Cbl-b phosphorylation assay, KIT and FcεRIα surface expression by flow cytometry, degranulation assay, comparison to human mast cell mechanism International Immunology Medium 25239131
2013 The CD72c allele is a hypofunctional allele for BCR signal inhibition and functions as a modifier gene that regulates Fas(lpr)-induced lupus-like autoimmune disease. Introduction of the chromosomal interval containing Cd72c caused lupus-like disease on B6/lpr background, while replacement of Cd72c with Cd72b in MRL/lpr congenic mice reduced disease severity. Congenic mouse generation, BCR signaling assays comparing CD72c vs CD72b, disease severity assessment (autoantibodies, CD4⁻CD8⁻ T cells) Journal of Immunology High 23616572
2025 Soluble CD72 (sCD72) binds to CD100 on the surface of T cells and enters the cytoplasm, suppressing T cell adaptive immune functions (reducing CD4+IFN-γ+, CD8+Perforin+, CD8+GZMB+, CD8+FASL+ populations and increasing CD4+TNF-α+ population) in a sepsis model. Recombinant sCD72 injection in CLP sepsis mouse model, flow cytometry of T cell subsets, confocal microscopy showing sCD72 entering T cell cytoplasm, CRISPR/Cas9 CD72-KO mice International Immunopharmacology Medium 39793226
2024 Soluble CD72 (sCD72) interacts with CD6 on activated CD4+ T cells (identified by mass spectrometry and co-immunoprecipitation) and increases pro-inflammatory cytokines (IL-17A, IFN-γ) and T cell proliferation, activating the SLP-76-AKT-mTOR pathway. Mass spectrometry, co-immunoprecipitation, flow cytometry for cytokine secretion, phosphorylation assay (SLP-76, AKT, mTOR), CFSE proliferation assay Frontiers in Immunology Medium 39026665

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1991 The B-cell surface protein CD72/Lyb-2 is the ligand for CD5. Nature 307 1711157
2000 Identification of CD72 as a lymphocyte receptor for the class IV semaphorin CD100: a novel mechanism for regulating B cell signaling. Immunity 296 11114375
1999 CD72-deficient mice reveal nonredundant roles of CD72 in B cell development and activation. Immunity 160 10549631
1998 The B cell surface protein CD72 recruits the tyrosine phosphatase SHP-1 upon tyrosine phosphorylation. Journal of immunology (Baltimore, Md. : 1950) 121 9590210
1998 The B-cell transmembrane protein CD72 binds to and is an in vivo substrate of the protein tyrosine phosphatase SHP-1. Current biology : CB 97 9740800
2001 The CD100-CD72 interaction: a novel mechanism of immune regulation. Trends in immunology 95 11738997
2003 Involvement of CD100, a lymphocyte semaphorin, in the activation of the human immune system via CD72: implications for the regulation of immune and inflammatory responses. International immunology 83 12882840
1989 Sequence of the Lyb-2 B-cell differentiation antigen defines a gene superfamily of receptors with inverted membrane orientation. Proceedings of the National Academy of Sciences of the United States of America 81 2645579
1983 On the function of Ly-5 in the regulation of antigen-driven B cell differentiation. Comparison and contrast with Lyb-2. The Journal of experimental medicine 79 6220106
2000 CD72 negatively regulates signaling through the antigen receptor of B cells. Journal of immunology (Baltimore, Md. : 1950) 75 10640734
1994 B-cell signalling via the C-type lectins CD23 and CD72. Immunology today 75 7945782
1992 Ly-1 (CD5), a membrane glycoprotein of mouse T lymphocytes and a subset of B cells, is a natural ligand of the B cell surface protein Lyb-2 (CD72). Journal of immunology (Baltimore, Md. : 1950) 67 1371783
2004 Molecular interactions regulate BCR signal inhibition by CD22 and CD72. Trends in immunology 66 15364057
2000 CD72, a negative regulator of B-cell responsiveness. Immunological reviews 60 11043769
1981 Lyb-2 system of mouse B cells. Evidence for a role in the generation of antibody-forming cells. The Journal of experimental medicine 60 6969779
2021 Surface Proteomics Reveals CD72 as a Target for In Vitro-Evolved Nanobody-Based CAR-T Cells in KMT2A/MLL1-Rearranged B-ALL. Cancer discovery 59 33727310
2022 Single-cell transcriptomic analyses of cardiac immune cells reveal that Rel-driven CD72-positive macrophages induce cardiomyocyte injury. Cardiovascular research 53 34100920
1990 Identification of a human protein homologous to the mouse Lyb-2 B cell differentiation antigen and sequence of the corresponding cDNA. Journal of immunology (Baltimore, Md. : 1950) 53 2141045
1996 Antigen receptor-mediated B cell death is blocked by signaling via CD72 or treatment with dextran sulfate and is defective in autoimmunity-prone mice. International immunology 50 8671676
1996 The CD5/CD72 receptor system is coexpressed with several functionally relevant counterstructures on human B cells and delivers a critical signaling activity. Journal of immunology (Baltimore, Md. : 1950) 46 8757302
1988 Properties of anti-Lyb-2-mediated B-cell activation and the relationship between Lyb-2 molecules and receptors for B-cell stimulatory factor-1 on murine B lymphocytes. Cellular immunology 42 3281760
2005 Requirement for CD100-CD72 interactions in fine-tuning of B-cell antigen receptor signaling and homeostatic maintenance of the B-cell compartment. International immunology 41 16113236
1998 CD72-mediated B cell activation involves recruitment of CD19 and activation of phosphatidylinositol 3-kinase. European journal of immunology 41 9808169
2008 Modulation of peripheral B cell tolerance by CD72 in a murine model. Arthritis and rheumatism 40 18821699
2016 CD72 negatively regulates B lymphocyte responses to the lupus-related endogenous toll-like receptor 7 ligand Sm/RNP. The Journal of experimental medicine 39 27810925
2008 CD72, a coreceptor with both positive and negative effects on B lymphocyte development and function. Journal of clinical immunology 38 19067131
1991 Stimulation of B lymphocytes via CD72 (human Lyb-2). European journal of immunology 38 1828426
1986 A role for Lyb-2 in B cell activation mediated by a B cell stimulatory factor. Journal of immunology (Baltimore, Md. : 1950) 37 3091682
2014 Interaction of CD5 and CD72 is involved in regulatory T and B cell homeostasis. Immunological investigations 36 24950378
1998 Activation of lyn, blk, and btk but not syk in CD72-stimulated B lymphocytes. Journal of immunology (Baltimore, Md. : 1950) 36 9531290
2013 A regulatory role for CD72 expression on B cells in systemic lupus erythematosus. Seminars in arthritis and rheumatism 33 24461079
2010 CD72 negatively regulates KIT-mediated responses in human mast cells. Journal of immunology (Baltimore, Md. : 1950) 33 20100931
2004 CD72 polymorphisms associated with alternative splicing modify susceptibility to human systemic lupus erythematosus through epistatic interaction with FCGR2B. Human molecular genetics 33 15459183
1992 Extensive polymorphism in the extracellular domain of the mouse B cell differentiation antigen Lyb-2/CD72. Journal of immunology (Baltimore, Md. : 1950) 33 1634777
2000 BLNK is associated with the CD72/SHP-1/Grb2 complex in the WEHI231 cell line after membrane IgM cross-linking. European journal of immunology 31 10820378
2006 CD72 down-modulates BCR-induced signal transduction and diminishes survival in primary mature B lymphocytes. Journal of immunology (Baltimore, Md. : 1950) 30 16621999
2001 Positive signaling through CD72 induces mitogen-activated protein kinase activation and synergizes with B cell receptor signals to induce X-linked immunodeficiency B cell proliferation. Journal of immunology (Baltimore, Md. : 1950) 30 11466342
2007 CD100 on NK cells enhance IFNgamma secretion and killing of target cells expressing CD72. PloS one 29 17786190
1981 Ly-m19: the Lyb-2 region of mouse chromosome 4 controls a new surface alloantigen. Immunogenetics 29 7287083
2013 Cd72(c) is a modifier gene that regulates Fas(lpr)-induced autoimmune disease. Journal of immunology (Baltimore, Md. : 1950) 25 23616572
1995 Structure of the mouse CD72 (Lyb-2) gene and its alternatively spliced transcripts. Journal of immunology (Baltimore, Md. : 1950) 25 7876545
1991 Identity of human Lyb-2 and CD72 and localization of the gene to chromosome 9. European journal of immunology 24 2044654
2018 CD72/CD100 and PD-1/PD-L1 markers are increased on T and B cells in HIV-1+ viremic individuals, and CD72/CD100 axis is correlated with T-cell exhaustion. PloS one 23 30161254
2017 Intact CD100-CD72 Interaction Necessary for TCR-Induced T Cell Proliferation. Frontiers in immunology 23 28713384
2007 Down-regulation of CD72 and increased surface IgG on B cells in patients with lupus nephritis. Autoimmunity 23 17364492
2002 Positive and negative roles of CD72 in B cell function. Immunologic research 23 11999169
1993 Expression of CD5 and CD72 on T and B cell subsets in rheumatoid arthritis and Sjögren's syndrome. Clinical and experimental immunology 23 7683586
1987 Early events in B-cell activation: anti-Lyb2, but not BSF-1, induces a phosphatidylinositol response in murine B cells. Cellular immunology 22 3499987
1982 Evidence that Lyb-2 is critical to specific activation of B cells before they become responsive to T cell and other signals. The Journal of experimental medicine 22 6175719
1992 Human Lyb-2 homolog CD72 is a marker for progenitor B-cell leukemias. American journal of hematology 21 1384316
1991 Differential regulation of surface Ig- and Lyb2-mediated B cell activation by cyclic AMP. I. Evidence for alternative regulation of signaling through two different receptors linked to phosphatidylinositol hydrolysis in murine B cells. Journal of immunology (Baltimore, Md. : 1950) 21 1717562
1988 Differential regulation by Ly-5 and Lyb-2 of IgG production induced by lipopolysaccharide and B cell stimulatory factor-1 (IL-4). Journal of immunology (Baltimore, Md. : 1950) 21 3260915
2023 Framework humanization optimizes potency of anti-CD72 nanobody CAR-T cells for B-cell malignancies. Journal for immunotherapy of cancer 20 38007238
1998 PU.1/Spi-1 is essential for the B cell-specific activity of the mouse CD72 promoter. Journal of immunology (Baltimore, Md. : 1950) 20 9498769
2004 Increased expression of the B-cell-regulatory molecule CD72 in primary Sjögren's syndrome. Tissue antigens 18 14989715
2019 CD72 is a Negative Regulator of B Cell Responses to Nuclear Lupus Self-antigens and Development of Systemic Lupus Erythematosus. Immune network 17 30838156
1992 Occupancy of CD72 (the CD5 counterstructure) enhances interleukin-4-dependent CD23 expression in resting B lymphocytes. Immunology 17 1388135
2005 Dual regulation of BCR-mediated growth inhibition signaling by CD72. European journal of immunology 16 15816000
2005 CD72-mediated suppression of human naive B cell differentiation by down-regulating X-box binding protein 1. European journal of immunology 16 16047337
2016 Increased soluble CD72 in systemic lupus erythematosus is in association with disease activity and lupus nephritis. Clinical immunology (Orlando, Fla.) 15 26883681
2009 B-cell co-receptor CD72 is expressed on NK cells and inhibits IFN-gamma production but not cytotoxicity. European journal of immunology 15 19197938
1992 Regulation of lipopolysaccharide- and IL-4-induced immunoglobulin heavy chain gene activation: differential roles for CD45 and Lyb-2. International immunology 15 1535509
2017 Upregulation of CD72 expression on CD19+ CD27+ memory B cells by CD40L in primary immune thrombocytopenia. British journal of haematology 14 28419421
2008 CD72 polymorphism associated with child-onset of idiopathic thrombocytopenic purpura in Chinese patients. Journal of clinical immunology 14 18071878
1997 Allele-specific expression of the mouse B-cell surface protein CD72 on T cells. Immunogenetics 14 8995186
2012 Placental expression of CD100, CD72 and CD45 is dysregulated in human miscarriage. PloS one 13 22606231
1993 Biochemical identity of the mouse Ly-19.2 and Ly-32.2 alloantigens with the B cell differentiation antigen Lyb-2/CD72. Journal of immunology (Baltimore, Md. : 1950) 13 8409435
2012 Human CD72 splicing isoform responsible for resistance to systemic lupus erythematosus regulates serum immunoglobulin level and is localized in endoplasmic reticulum. BMC immunology 11 23268649
2006 Increased mutations of CD72 transcript in B-lymphocytes from adolescent patients with systemic lupus erythematosus. Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology 11 17121583
2004 Impairment of B cell receptor-mediated Ca2+ influx, activation of mitogen-activated protein kinases and growth inhibition in CD72-deficient BAL-17 cells. International immunology 11 15148289
2003 Structure and function of CD72 in the non-obese diabetic (NOD) mouse. Autoimmunity 11 14563017
2020 A regulatory role for CD72 expression on B cells and increased soluble CD72 in primary Sjogren's syndrome. BMC immunology 10 32306893
2019 CD22 and CD72 contribute to the development of scleroderma in a murine model. Journal of dermatological science 10 31883832
1997 Modulation of CD72 by ligation of B cell receptor complex molecules on CD5+ B cells. International immunology 10 9237109
1995 An anti-CD72 immunotoxin against therapy-refractory B-lineage acute lymphoblastic leukemia. Leukemia & lymphoma 10 8580813
1988 Biochemical similarity of Ly-19, Ly-32, and Lyb-2 alloantigens encoded in the gene cluster on mouse chromosome 4. Immunogenetics 10 3169880
2013 Modulation of B cell regulatory molecules CD22 and CD72 in myasthenia gravis and multiple sclerosis. Inflammation 9 23184497
1993 Differential regulation of surface immunoglobulin and Lyb2 mediated B cell activation: II. cAMP dependent (prostaglandin E2) and independent (IFN-gamma) mechanisms of regulation of B lymphocyte activation. International immunology 9 8398988
2022 CD72-semaphorin3A axis: A new regulatory pathway in systemic lupus erythematosus. Journal of autoimmunity 8 36470209
2018 CD100/Sema4D Increases Macrophage Infection by Leishmania (Leishmania) amazonensis in a CD72 Dependent Manner. Frontiers in microbiology 8 29922261
2017 Interferon-α-induced CD100 on naïve CD8+ T cells enhances antiviral responses to hepatitis C infection through CD72 signal transduction. The Journal of international medical research 8 28222623
2013 CD72 regulates the growth of KIT-mutated leukemia cell line Kasumi-1. Scientific reports 8 24713856
2014 CD72 negatively regulates mouse mast cell functions and down-regulates the expression of KIT and FcεRIα. International immunology 7 25239131
2006 A novel avian homologue of CD72, chB1r, down modulates BCR-mediated activation signals. International immunology 7 16581823
2004 CD72 stimulation modulates anti-IgM induced apoptotic signaling through the pathway of NF-kappaB, c-Myc and p27(Kip1). Microbiology and immunology 7 14734859
1997 CD72 ligation regulates defective naive newborn B cell responses. Cellular immunology 7 9023424
2013 A bacterial artificial chromosome transgene with polymorphic Cd72 inhibits the development of glomerulonephritis and vasculitis in MRL-Faslpr lupus mice. Journal of immunology (Baltimore, Md. : 1950) 6 23365086
1987 B-cell activation stimulated by monoclonal anti-Lyb2.1 antibody is mediated through a receptor distinct from the BSF-1 receptor. Cellular immunology 6 2957071
2024 Asiaticoside alleviates lipopolysaccharide-induced acute lung injury by blocking Sema4D/CD72 and inhibiting mitochondrial dysfunction in RAW264.7 cell and mice. Naunyn-Schmiedeberg's archives of pharmacology 5 38664244
1993 Stimulation of tyrosine phosphorylation without inositol lipid hydrolysis in human B lymphocytes on engaging CD72. FEBS letters 5 7681409
2024 Soluble CD72, is a T-cell activator probably via binding to CD6 in homeostasis and autoimmunity. Frontiers in immunology 4 39026665
2025 Soluble CD72 concurrently impairs T cell functions while enhances inflammatory response in sepsis. International immunopharmacology 3 39793226
2024 Integrative transcriptomic analysis reveals Cd72 as a novel pro-inflammatory factor in microglia following experimental ischemic stroke. Experimental neurology 3 39326825
2019 CD22 and CD72 cooperatively contribute to the development of the reverse Arthus reaction model. Journal of dermatological science 3 31262443
2009 Centromeric interval of chromosome 4 derived from C57BL/6 mice accelerates type 1 diabetes in NOD.CD72b congenic mice. Biochemical and biophysical research communications 3 19167349
2006 Various domains of the B-cell regulatory molecule CD72 has diverged at different rates in mammals: cloning, transcription and mapping of porcine CD72. Developmental and comparative immunology 3 17023047
2001 R-phycoerythrin-cyanine 5 tandem discerns CD72 polymorphism. Immunogenetics 3 11491534
2023 CD72 is a pan-tumor antigen associated to pediatric acute leukemia. Cytometry. Part A : the journal of the International Society for Analytical Cytology 2 37876342
2022 Blockage of CD72 reduces B cell proliferation in immune thrombocytopenic purpura, involving interleukin 1 and macrophage migration inhibitory factor secretion. Hematology (Amsterdam, Netherlands) 2 36326455
1998 Selective response of CD5+ B cell malignancies to activation of the CD72 antigen. Clinical immunology and immunopathology 2 9576009

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