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Targets Associated to Immuno Cell Types - B cells

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The B cells category includes the following Cell Ontology parent terms:

lymphocyte of B lineage (CL:0000945) - A lymphocyte of B lineage is a lymphocyte that expresses CD19 on the cell surface. An additional defining characteristic is the commitment to express an immunoglobulin complex. Types of B lineage lymphocytes include B cells and antibody secreting cells (plasmablasts and plasma cells). Lymphocytes of B cell lineage can be distinguished from those of T cell lineage by their lack of CD3e (as part of the T cell receptor complex).

GPCRs
GtoPdb receptor name (family) Cell Type Association Comments Cell Ontology Associations Immunopharmacology Comments
β2-adrenoceptor
(Adrenoceptors)
B cells from patients with rheumatoid arthritis express lower levels of β2-ARs compared with healthy subjects.
  • B cell (CL:0000236)
β2-ARs are expressed on innate and adaptive immune cells of humans and rodents, and are reported to have an immuno-modulating effect [40] ...
5-HT1A receptor
(5-Hydroxytryptamine receptors)
  • B cell (CL:0000236)
The chemoattractant properties of 5-HT on both human and mouse mast cells are mediated by 5-HT1A receptor [72] ...
5-HT2A receptor
(5-Hydroxytryptamine receptors)
  • B cell (CL:0000236)
The chemoattractant properties of 5-HT on human eosinophils is mediated by 5-HT2A receptor [16] ...
5-HT7 receptor
(5-Hydroxytryptamine receptors)
  • B cell (CL:0000236)
5-HT has been shown to alter cytokine production by dendritic cells via 5-HT4 and 5-HT7 receptors [3] ...
FFA3 receptor
(Free fatty acid receptors)
    FFA3 has been included in GtoImmuPdb as its expression has been detected in immune cells [19] ...
    CXCR3
    (Chemokine receptors)
    • B cell (CL:0000236)
    CXCR3 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. CXCR3 is the receptor for CXCL9, -10 and -11, three CXC chemokines that are preferentially expressed on Th1 lymphocytes.
    S1P1 receptor
    (Lysophospholipid (S1P) receptors)
    B- and T-lymphocytes predominantly express S1P1 receptors, with S1P3 and S1P4 expressed at lower levels.
    • B cell (CL:0000236)
    S1P1R activation by agonists downregulates allergic inflammation (i.e. it has an inhibitory effect) [56,58,106] ...
    Ion Channels
    GtoPdb receptor name (family) Cell Type Association Comments Cell Ontology Associations Immunopharmacology Comments
    P2X1
    (P2X receptors)
    Human B cells express all P2 receptor subtypes.
      Functional P2X1 receptors are expressed by healthy human eosinophils [134] ...
      P2X2
      (P2X receptors)
      Human B cells express all P2 receptor subtypes.
      • B cell (CL:0000236)
      P2X ligand-gated ion channels elicit pro-inflammatory immune responses upon activation by extracellular ATP that acts as a DAMP when released from damaged or infected cells [21,25] ...
      P2X3
      (P2X receptors)
      Human B cells express all P2 receptor subtypes.
      • B cell (CL:0000236)
      P2X ligand-gated ion channels elicit pro-inflammatory immune responses upon activation by extracellular ATP that acts as a DAMP when released from damaged or infected cells [21,25] ...
      P2X4
      (P2X receptors)
      Human B cells express all P2 receptor subtypes.
      • B cell (CL:0000236)
      P2X ligand-gated ion channels elicit pro-inflammatory immune responses upon activation by extracellular ATP that acts as a DAMP when released from damaged or infected cells [21,25] ...
      P2X5
      (P2X receptors)
      Human B cells express all P2 receptor subtypes.
      • B cell (CL:0000236)
      P2X ligand-gated ion channels elicit pro-inflammatory immune responses upon activation by extracellular ATP that acts as a DAMP when released from damaged or infected cells [21,25] ...
      P2X6
      (P2X receptors)
      Human B cells express all P2 receptor subtypes.
      • B cell (CL:0000236)
      P2X ligand-gated ion channels elicit pro-inflammatory immune responses upon activation by extracellular ATP that acts as a DAMP when released from damaged or infected cells [21,25] ...
      P2X7
      (P2X receptors)
      Human B cells express all P2 receptor subtypes.
      • B cell (CL:0000236)
      The P2X7 receptor is involved in NLRP3-type inflammasome formation, and subsequent maturation of IL-1β [76,100] ...
      TRPM7
      (Transient Receptor Potential channels)
      TRPM7 is expressed by B cells.
      • B cell (CL:0000236)
      Expressed on chicken B cells, mouse T cells, chicken monocytes/macrophages, and human mast cells [94] ...
      Hv1
      (Voltage-gated proton channel)
      Hv1 participates in B cell activation, ROS production and antibody responses.
      • B cell (CL:0000236)
      Detection of low intracellular pH by the Hv1 ion channel impacts upon the function of B cells, macrophages, neutrophils and microglia [24,124] ...
      Enzymes
      GtoPdb receptor name (family) Cell Type Association Comments Cell Ontology Associations Immunopharmacology Comments
      TRPM7
      (Transient Receptor Potential channels)
      TRPM7 is expressed by B cells.
      • B cell (CL:0000236)
      Expressed on chicken B cells, mouse T cells, chicken monocytes/macrophages, and human mast cells [94] ...
      mitogen-activated protein kinase kinase kinase kinase 1
      (KHS subfamily)
      • B cell (CL:0000236)
      HPK1 inhibits T-cell receptor (TCR) signaling via a mechanism that induces phosphorylation and ubiquitination of SLP-76, it inhibits B-cell receptor signaling by inducing phosphorylation and ubiquitination of BLNK [129] ...
      mitogen-activated protein kinase kinase kinase kinase 2
      (KHS subfamily)
      Expression of GCK in lymphoid follicles is restricted to germinal center B cells.
      • germinal center B cell (CL:0000844)
      In vitro analyses suggest that GCK plays important roles in the innate immune response and cell signalling [30] ...
      mitogen-activated protein kinase kinase kinase kinase 4
      (MSN subfamily)
      • B cell (CL:0000236)
      HGK is widely expressed in different tissues. In vitro, HGK is activated by TNFα stimulation, and this results in JNK activation via the MAP3K, TAK1 (MAP3K7) and the MAP2Ks, MKK4 (MAP2K4) and MKK7 (MAP2K7) [37,116,120] ...
      BLK proto-oncogene, Src family tyrosine kinase
      (Src family)
      BLK is only expressed in B cells.
      • B cell (CL:0000236)
      BLK is a B cell-specific kinase. In Blk knockout mice B cells develop normally and show unaltered in vitro activation and humoral immune responses to T cell-dependent and -independent antigens, a result which is indicative of functional redundancy of Blk in B cell development and immune responses [122] ...
      FGR proto-oncogene, Src family tyrosine kinase
      (Src family)
      Primarily in mantle zone B cells,
      • B cell (CL:0000236)
      Fgr may be involved in neutrophil migration, potentially via binding to intergrins [14] ...
      FYN proto-oncogene, Src family tyrosine kinase
      (Src family)
      • B cell (CL:0000236)
      Animal models and cell line studies indicate a critical role for Fyn in proximal T-cell antigen receptor (TCR) signal transduction [92] ...
      LYN proto-oncogene, Src family tyrosine kinase
      (Src family)
      • B cell (CL:0000236)
      LYN is a Src family tyrosine kinase, expressed predominantly in hematopoietic cells, but also in neural, liver, and adipose tissues. LYN appears to function as a rheostat to modulate B cell signaling, and can be activating or inhibitory in action, depending on the B cell receptor and interacting protein complement present in particular cells [44,46,123] ...
      YES proto-oncogene 1, Src family tyrosine kinase
      (Src family)
      Low expression level
      • B cell (CL:0000236)
      Although primarily recognised for its oncogenic activity, we have iincluded YES1 in GtoImmuPdb based on its expression in cells of the immune system.
      Bruton tyrosine kinase
      (Tec family)
      BTK is essential for B lymphocyte development, differentiation and signalling, playing an important role in the function of innate immune cells and the adaptive immune response. BTK is involved in cytokine signalling and is a component of the Toll-like receptors (TLR) pathway (linking TLR activation to induction of NF-κB, and downstream cytokine regulation).
        The TEC family protein tyrosine kinases have been identified as key components of T-cell-receptor activation and signalling. TEC family kinases are expressed predominantly by haematopoietic cells. T cells express ITK, TXK and TEC [15] ...
        phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta
        (Phosphatidylinositol-4,5-bisphosphate 3-kinase family)
        • B cell (CL:0000236)
        PI3Kδ is preferentially expressed in cells of hemopoietic lineage and is involved in neutrophil chemotaxis. It is the only PI3K isoform with expression restricted to leukocytes. Genetic and pharmacological inactivation of PI3Kδ indicates its importantance for the function of T cells, B cell, mast cells and neutrophils. PI3kδ is a promising target for drugs for preventing or treating inflammation, autoimmunity and transplant rejection [52] ...
        phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta
        (Phosphatidylinositol-4,5-bisphosphate 3-kinase family)
        • B cell (CL:0000236)
        PI3Kδ is preferentially expressed in cells of hemopoietic lineage and is involved in neutrophil chemotaxis. It is the only PI3K isoform with expression restricted to leukocytes. Genetic and pharmacological inactivation of PI3Kδ indicates its importantance for the function of T cells, B cell, mast cells and neutrophils. PI3kδ is a promising target for drugs for preventing or treating inflammation, autoimmunity and transplant rejection [52] ...
        Catalytic Receptors
        GtoPdb receptor name (family) Cell Type Association Comments Cell Ontology Associations Immunopharmacology Comments
        CD30
        (Tumour necrosis factor (TNF) receptor family)
        CD30 is expressed by activated, but not by resting, T and B cells.
          Expressed by activated T and B cells. Interacts with TRAF2 and TRAF5 to elicit downstream signalling events (NF-κB activation). CD30 may protect against autoimmunity by limiting the proliferative potential of autoreactive CD8 effector T cells. CD30 is the target of the approved anti-lymphoma monoclonal antibody drug brentuximab vedotin ...
          Other Protein Targets
          GtoPdb receptor name (family) Cell Type Association Comments Cell Ontology Associations Immunopharmacology Comments
          CD86
          (CD molecules)
          • B cell (CL:0000236)
          CD86 (B7-2) is a type I membrane immunoglobulin. It is expressed on antigen-presenting cells and in association with CD80 provides the costimulatory signal necessary for T cell activation and survival. CD86 interacts with CD28 or CTLA-4 on T cells. It is the interaction with CTLA-4 that is targeted ...
          programmed cell death 1 (CD279)
          (CD molecules)
          Expressed in pro-B cells and is thought to play a role in their differentiation. PD-1 expression is induced in murine B cells activated by stimulation through antigen receptors.
          • B cell (CL:0000236)
          • Fraction C precursor B cell (CL:0002049)
          Immune checkpoint blockade in oncology:
          Many types of cancer cells evolve mechanisms to evade control and elimination by the immune system. Such mechanisms can include inhibition of so-called 'immune checkpoints', which would normally be involved in the maintenance of immune homeostasis. An increasingly important area of clinical oncology research is the development of new agents which impede these evasion techniques, thereby switching immune vigilance back on, and effecting immune destruction of cancer cells. Three molecular targets of checkpoint inhibitors which are being extensively pursued are cytotoxic T-lymphocyte antigen 4 (CTLA4), programmed cell death 1 (PD-1), and programmed cell death ligand 1 (PD-L1). Using antibody-based therapies targeting these pathways, clinical responses have been reported in various tumour types, including melanoma, renal cell carcinoma [91] ...
          CD80
          (CD molecules)
          • B cell (CL:0000236)
          CD80 (B7-1) is expressed on dendritic cells and activated B cells and monocytes. It is required to provide a costimulatory signal necessary for T cell activation and survival. CD80 works in concert with CD86 to prime T cells. CD80 binds CD28 and CTLA-4 on T cells. It is the interaction with CTLA-4 t ...
          CD22
          (CD molecules)
          • B cell (CL:0000236)
          CD22 (SIGLEC-2) is a B cell I-type (Ig-type) lectin that binds glycans containing sialic acids. It is involved in adhesion and activation. Mediates B cell-B cell interactions and may be involved in the localization of B cells in lymphoid tissues. Most SIGLECs inhibit immune cell activation, via
          Fc fragment of IgM receptor
          (Immunoglobulin like domain containing proteins)
          Upregulated expression of FcμRI renders malignant B cells in chronic lymphocytic leukemia (CLL) resistant to apoptosis, and leads to their accumulation.
          • B cell (CL:0000236)
          FcμRI is the cognate Fc receptor for immunoglobulin M (IgM) [71,78,112] ...
          CD4
          (CD molecules)
          • B cell (CL:0000236)
          CD4 is being targeted for clinical utility in inflammatory diseases like rheumatoid arthritis (RA), neoplasms derived from T helper cells (T cell lymphomas and related malignancies), and for anti-HIV potential. Depending on the design of CD4 targeting antibodies, they can porduce immunosuppressive effects via activation of Tregs and induction of tolerance, block HIV binding to CD4 to prevent HIV infection, or induce depletion of CD4+ T cells by apoptosis, ADCC, or CDC [70,127] ...
          CD19
          (CD molecules)
          • B cell (CL:0000236)
          CD19 is a B cell antigen used as a biomarker for normal and neoplastic B cells, and follicular dendritic cells. Anti-CD19 monoclonal antibodies are being investigated for potential clinical utility in oncology, transplantation and autimmune diseases (e.g. inebilizumab ...
          CD2
          (CD molecules)
            CD2 is a cell surface glycoprotein expressed on most human T cells and natural killer (NK) cells [135] ...
            leukocyte immunoglobulin like receptor B1 (CD85j)
            (CD molecules)
            Loss of LILRB1 on malignant plasma cells plays a role in immune escape in multiple myeloma. In contrast, overexpression of LILRB1 increases susceptibility to T cell- and NK-mediated killing.
            • plasma cell (CL:0000786)
            LILRB1 (CD85j) is a member of the inhibitory leukocyte immunoglobulin like receptor (LILRB) family (HGNC family 1182). It acts as an inhibitory immune checkpoint for B cell function. Ligands identified for LILRB include native MHC class I proteins, some HLA molecules, pathogen-derived ligands (e.g. from CMV, Dengue virus and some bacteria) and host immunomodulatory proteins such as S100 calcium binding protein A9 (S100A9; P06702; which also binds TLR4 and RAGE) [22] ...
            CD20 (membrane-spanning 4-domains, subfamily A, member 1)
            (CD molecules)
            • B cell (CL:0000236)
            CD20 is a B cell antigen, involved in B cell development and maturation to antibody-producing plasma cells [32] ...
            CD37 molecule
            (CD molecules)
            CD37 is more highly expressed by mature B cells than by T cells or myeloid cells. It is not expressed by CD10+, CD34+ and CD34- B cell precursors in the bone marrow. Expression is lost in terminally differentiated plasma cells. CD37 is minimally detectable on T cells, monocytes and granulocytes, and is not expressed by natural killer (NK) cells, platelets or erythrocytes. CD37 is highly expressed by transformed mature B cell leukemia and lymphoma cells but not by myeloma cells.
            • mature B cell (CL:0000785)
            CD37 is included in GtoImmuPdb as it is an immuno-oncology target that is being expoited for the development of novel therapeutics for the treatment of B cell malignancies, including non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL) [34,90,115,133] ...
            CS1 (CD319)
            (CD molecules)
            • plasma cell (CL:0000786)
            CS1 is a member of the signalling lymphocyte activation molecule (SLAM) receptor family. CS1 is a membrane glycoprotein primarily expressed on plasma cells. Homophilic interaction (i.e. interaction with itself) of CS1 induces B cell proliferation and autocrine cytokine secretion, thus playing a role in various immune functions.

            CS1 is a validated molecular target for the development of novel immunotherapeutics with the potential to treat MM, a malignant disease of plasma cells which remains incurable despite advances in treatment (such as bortezomib, lenalidomide and immunotherapies in clinical trial). Indeed, a combination therapy containing the anti-CS1 mAb elotuzumab (elotuzumab + lenalidomide + dexamethasone), was FDA approved for MM in 2015. CS1 expression is also elevated in patients with systemic lupus erythematosus (SLE) [68] ...
            CD6
            (CD molecules)
              CD6 is a co-stimulatory molecule, predominantly expressed on lymphocytes and associated with autoimmune responses. CD6 interacts with activated leucocyte-cell adhesion molecule (ALCAM/CD166), found on antigen presenting cells. This interaction induces the production of proinflammatory cytokines [88] ...
              leukocyte immunoglobulin like receptor B1 (CD85j)
              (CD molecules)
              Loss of LILRB1 on malignant plasma cells plays a role in immune escape in multiple myeloma. In contrast, overexpression of LILRB1 increases susceptibility to T cell- and NK-mediated killing.
              • plasma cell (CL:0000786)
              LILRB1 (CD85j) is a member of the inhibitory leukocyte immunoglobulin like receptor (LILRB) family (HGNC family 1182). It acts as an inhibitory immune checkpoint for B cell function. Ligands identified for LILRB include native MHC class I proteins, some HLA molecules, pathogen-derived ligands (e.g. from CMV, Dengue virus and some bacteria) and host immunomodulatory proteins such as S100 calcium binding protein A9 (S100A9; P06702; which also binds TLR4 and RAGE) [22] ...
              regulator of G-protein signaling 1
              (R4 family)
                RGS1 is expressed in lymphocytes and macrophages and plays a role in leukocyte trafficking and vascular inflammation [17,50,86,95] ...
                regulator of G-protein signaling 13
                (R4 family)
                • B cell (CL:0000236)
                RGS13 inhibits CXCL12- and CXCL13-induced MAPK activation, and chemotaxis [111] ...
                C-type lectin domain family 4 member E
                (C-type lectin-like receptors (CLRs))
                • B cell (CL:0000236)
                Mincle is an FcRγ-associated membrane receptor involved in initiating the innate immune response upon recognition of endogenous and exogenous ligands including Sin3A-associated protein (SAP130), α-mannan on fungal cell walls and mycobacterial cord factor (trehalose-6,6′-dimycolate (TDM)) [20] ...
                Fc fragment of IgE receptor II
                (Fc epsilon receptors)
                • B cell (CL:0000236)
                FcεRII (CD23) is the low-affinity receptor for immunoglobulin E (IgE) with a Kd > 100nM. This protein is a C-type lectin found on mature B cells, activated macrophages, eosinophils, follicular dendritic cells, and platelets. It has no structural similarities with other Fc receptors. FcεRII has functions as both a membrane-bound and as a soluble receptor [66,136] ...
                CD22
                (CD molecules)
                • B cell (CL:0000236)
                CD22 (SIGLEC-2) is a B cell I-type (Ig-type) lectin that binds glycans containing sialic acids. It is involved in adhesion and activation. Mediates B cell-B cell interactions and may be involved in the localization of B cells in lymphoid tissues. Most SIGLECs inhibit immune cell activation, via
                CD22
                (CD molecules)
                • B cell (CL:0000236)
                CD22 (SIGLEC-2) is a B cell I-type (Ig-type) lectin that binds glycans containing sialic acids. It is involved in adhesion and activation. Mediates B cell-B cell interactions and may be involved in the localization of B cells in lymphoid tissues. Most SIGLECs inhibit immune cell activation, via
                CD38
                (CD molecules)
                  CD38 is a type II transmembrane glycoprotein, that is widely expressed on immune cells and is involved in cell adhesion and signal transduction. Its extracellular domain acts as an ectoenzyme, catalyzing the conversion of nicotinamide adenine dinucleotide (NAD+) into nicotinamide, adenosine diphosphate-ribose (ADPR), and cyclic ADPR. Expression of CD38 is tightly regulated during B-cell development and maturation [48] ...
                  CD52
                  (CD molecules)
                    CD52 (CAMPATH-1) is a short, glycosylphosphatidylinositol (GPI) anchored peptide expressed on lymphocytes and by cells of the male genital tract. CD52 is required for complement-mediated cell lysis and antibody-mediated cellular cytotoxicity. The approved monoclonal antibody, alemtuzumab ...
                    CD79B
                    (CD molecules)
                      CD79B is a component of the multimeric B cell antigen receptor (along with CD79A and a membrane-bound antibody that acts as the antigen recognition moiety). The CD79A/B component is responsible for signal transduction. The B cell antigen receptor complex is reported to be involved in the pathogenesis of various B cell-derived lymphoid cancers [87,108] ...
                      CD80
                      (CD molecules)
                      • B cell (CL:0000236)
                      CD80 (B7-1) is expressed on dendritic cells and activated B cells and monocytes. It is required to provide a costimulatory signal necessary for T cell activation and survival. CD80 works in concert with CD86 to prime T cells. CD80 binds CD28 and CTLA-4 on T cells. It is the interaction with CTLA-4 t ...
                      CD86
                      (CD molecules)
                      • B cell (CL:0000236)
                      CD86 (B7-2) is a type I membrane immunoglobulin. It is expressed on antigen-presenting cells and in association with CD80 provides the costimulatory signal necessary for T cell activation and survival. CD86 interacts with CD28 or CTLA-4 on T cells. It is the interaction with CTLA-4 that is targeted ...
                      programmed cell death 1 (CD279)
                      (CD molecules)
                      Expressed in pro-B cells and is thought to play a role in their differentiation. PD-1 expression is induced in murine B cells activated by stimulation through antigen receptors.
                      • B cell (CL:0000236)
                      • Fraction C precursor B cell (CL:0002049)
                      Immune checkpoint blockade in oncology:
                      Many types of cancer cells evolve mechanisms to evade control and elimination by the immune system. Such mechanisms can include inhibition of so-called 'immune checkpoints', which would normally be involved in the maintenance of immune homeostasis. An increasingly important area of clinical oncology research is the development of new agents which impede these evasion techniques, thereby switching immune vigilance back on, and effecting immune destruction of cancer cells. Three molecular targets of checkpoint inhibitors which are being extensively pursued are cytotoxic T-lymphocyte antigen 4 (CTLA4), programmed cell death 1 (PD-1), and programmed cell death ligand 1 (PD-L1). Using antibody-based therapies targeting these pathways, clinical responses have been reported in various tumour types, including melanoma, renal cell carcinoma [91] ...