Details for: TNFRSF13B

Gene ID: 23495

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: TNFRSF13B

Ensembl ID: ENSG00000240505

Description: TNF receptor superfamily member 13B

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 29.79
    rCSI 36.1%
    PRS 90.98
  • helper T cell CL0000912
    CSI 29.67
    rCSI 41.96%
    PRS 96.54
  • plasmablast CL0000980
    CSI 29.64
    rCSI 23.32%
    PRS 98.7
  • memory B cell CL0000787
    CSI 19.62
    rCSI 19.38%
    PRS 99.19
  • unswitched memory B cell CL0000970
    CSI 18.16
    rCSI 15.28%
    PRS 99.61
  • IgA plasma cell CL0000987
    CSI 18.14
    rCSI 18.57%
    PRS 97.68
  • conventional dendritic cell CL0000990
    CSI 14.61
    rCSI 12.19%
    PRS 95.68
  • IgG plasma cell CL0000985
    CSI 13.98
    rCSI 16.74%
    PRS 98.65
  • innate lymphoid cell CL0001065
    CSI 12.63
    rCSI 26.07%
    PRS 96.23
  • transitional stage B cell CL0000818
    CSI 12.26
    rCSI 40.13%
    PRS 99.67
  • fraction A pre-pro B cell CL0002045
    CSI 10.99
    rCSI 12.58%
    PRS 99.41
  • mature B cell CL0000785
    CSI 8.37
    rCSI 7.28%
    PRS 99.76
  • class switched memory B cell CL0000972
    CSI 5.59
    rCSI 4.18%
    PRS 99.38
  • cytotoxic T cell CL0000910
    CSI 5.42
    rCSI 31.04%
    PRS 96.94
  • melanocyte of skin CL1000458
    CSI 4.47
    rCSI 6.1%
    PRS 89.09
  • antibody secreting cell CL0000946
    CSI 3.25
    rCSI 14.44%
    PRS 99.67
  • basal cell of epidermis CL0002187
    CSI 2.63
    rCSI 4.66%
    PRS 87.66
  • IgM plasma cell CL0000986
    CSI 2.51
    rCSI 11.3%
    PRS 99.44

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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  • Node Color (Target Cell CSI, relative to current network):
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    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [TNFRSF13B](/details-gene/23495), also known as TACI (Transmembrane Activator and CAML Interactor), is a protein-coding gene located on chromosome 17p11.2. As a member of the tumor necrosis factor receptor superfamily, it functions as a critical cell surface receptor in the immune system. Expression data reveals its profound significance in the regulation of humoral immunity, with remarkably high expression and functional importance in various B cell subsets, including [plasmablasts](/details-cell/CL0000980) and [memory B cells](/details-cell/CL0000787), as well as in T cell populations. Functionally, it is integral to the `[adaptive immune response](/details-go/GO:0002250)` and `[B cell homeostasis](/details-go/GO:0001782)`, mediating signals upon binding its ligands, APRIL and BLyS (BAFF). Mutations in [TNFRSF13B](/details-gene/23495) are clinically associated with common variable immunodeficiency (CVID) and IgA deficiency, highlighting its essential role in antibody production and B cell function ([Link](https://doi.org/10.1038/ng1601)). ## Cellular Roles and Expression Landscape The expression profile of [TNFRSF13B](/details-gene/23495) firmly establishes it as a key regulator within the adaptive immune system, particularly in the B lymphocyte lineage. **Overall**, the gene shows its highest significance in terminally differentiated B cells and memory lymphocyte populations. The most significant expression is observed in cells central to humoral immunity. It is a top marker for [plasmablasts](/details-cell/CL0000980) (CSI: 29.64), [memory B cells](/details-cell/CL0000787) (CSI: 19.62), [IgA plasma cells](/details-cell/CL0000987) (CSI: 18.14), and [IgG plasma cells](/details-cell/CL0000985) (CSI: 13.98). This pattern suggests that [TNFRSF13B](/details-gene/23495) is not only involved in the initial stages of B cell development, as shown by its relevance in [transitional stage B cells](/details-cell/CL0000818), but plays an increasingly crucial role in the survival and function of long-lived antibody-secreting cells and memory compartments. Interestingly, [TNFRSF13B](/details-gene/23495) also demonstrates very high significance in T cell subsets, including [CD8-positive, alpha-beta memory T cells, CD45RO-positive](/details-cell/CL0001203) (CSI: 29.79) and [helper T cells](/details-cell/CL0000912) (CSI: 29.67). This dual-expression pattern in both B and T cell lineages points towards a potential role in mediating lymphocyte crosstalk, which is essential for coordinating adaptive immune responses. The gene's high significance in [conventional dendritic cells](/details-cell/CL0000990) (CSI: 14.61) further supports its role at the interface of innate and adaptive immunity. The collective expression data paints a picture of a gene specialized for regulating mature lymphocyte function and differentiation. ## Pathways and Molecular Function The molecular functions of [TNFRSF13B](/details-gene/23495) are deeply integrated with immune signaling pathways. As annotated, it participates in the `[cell surface receptor signaling pathway](/details-go/GO:0007166)` and exhibits `[signaling receptor activity](/details-go/GO:0038023)`. It is a well-characterized component of the `[Cytokine signaling in immune system](/details-reactome/R-HSA-1280215)` pathway, acting as a high-affinity receptor for the TNF family ligands APRIL (A Proliferation-Inducing Ligand) and BLyS/BAFF (B Lymphocyte Stimulator) ([Link](https://doi.org/10.1074/jbc.m005224200)). Upon ligand binding, [TNFRSF13B](/details-gene/23495) is known to engage TRAF adapter proteins, leading to the activation of downstream signaling cascades, including the `[Tnfr2 non-canonical nf-kb pathway](/details-reactome/R-HSA-5668541)` ([Link](https://doi.org/10.1084/jem.192.1.137)). This signaling is critical for its biological effects, which include promoting `[B cell homeostasis](/details-go/GO:0001782)` and, paradoxically, the `[negative regulation of b cell proliferation](/details-go/GO:0030889)`. This dual role suggests that [TNFRSF13B](/details-gene/23495) signaling is context-dependent, helping to fine-tune the balance between B cell survival, differentiation into plasma cells, and the termination of proliferative responses. Its function is therefore essential for generating effective, long-lasting antibody responses while preventing uncontrolled B cell expansion. ## Research Directions The established link between [TNFRSF13B](/details-gene/23495) mutations and immunodeficiencies like CVID provides a strong foundation for further investigation into its precise role in lymphocyte function and pathology. ### Proposed Hypotheses 1. **Hypothesis on T-B Crosstalk:** Given the high significance of [TNFRSF13B](/details-gene/23495) in both [helper T cells](/details-cell/CL0000912) and multiple B cell subsets, it is hypothesized that [TNFRSF13B](/details-gene/23495) expressed on B cells acts as a critical co-stimulatory receptor during T cell-dependent B cell activation, and its dysfunction directly impairs isotype switching and the formation of long-lived plasma cells. 2. **Hypothesis on Plasma Cell Survival:** The gene's exceptionally high significance in [plasmablasts](/details-cell/CL0000980) and plasma cells suggests that sustained [TNFRSF13B](/details-gene/23495) signaling is a key survival factor for these terminally differentiated cells. It is hypothesized that aberrant upregulation of this pathway contributes to the pathogenesis of plasma cell dyscrasias, such as multiple myeloma, by promoting tumor cell survival and resistance to apoptosis. ### Key Experiment To test the hypothesis regarding T-B crosstalk, a functional assay using CRISPR-Cas9 gene editing could be employed. Primary naive B cells would be isolated from healthy human donors and subjected to CRISPR-Cas9-mediated knockout of [TNFRSF13B](/details-gene/23495). These knockout B cells, along with wild-type controls, would then be co-cultured with allogeneic CD4+ [helper T cells](/details-cell/CL0000912) in the presence of a T-dependent stimulus (e.g., anti-CD40 and IL-4). After several days, the cultures would be assessed for B cell proliferation (by dye dilution), differentiation into [plasmablasts](/details-cell/CL0000980) (CD19+CD27++CD38++ phenotype by flow cytometry), and immunoglobulin class-switching (by measuring secreted IgG and IgA levels via ELISA). A significant reduction in these outcomes in the knockout group compared to the control would confirm the essential role of [TNFRSF13B](/details-gene/23495) in T cell-dependent B cell responses. ### Therapeutic Potential As a cell surface receptor predominantly expressed on lymphocytes, [TNFRSF13B](/details-gene/23495) represents a highly attractive therapeutic target. The therapeutic strategy would depend on the clinical context. In autoimmune diseases characterized by autoantibody production (e.g., systemic lupus erythematosus), where B cell and plasma cell activity is pathogenic, a strategy of **inhibition** would be appropriate. This could be achieved using a monoclonal antibody that blocks the binding of APRIL and BLyS to [TNFRSF13B](/details-gene/23495), thereby dampening B cell survival and antibody production. Conversely, for certain immunodeficiencies caused by loss-of-function mutations, a therapeutic **activation** approach using a recombinant ligand or an agonist antibody could potentially be explored to restore B cell function and antibody synthesis, though this would require careful management to avoid inducing autoimmunity.

Genular Protein ID: 3307364853

Symbol: TR13B_HUMAN

Name: Tumor necrosis factor receptor superfamily member 13B

UniProtKB Accession Codes:

O14836 B2R8B0 B7Z6V8 Q32LX4 Q7Z6F5

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChiTaRS 1 DIP 1 DNASU 1 DisGeNET 1 EMBL 6 Ensembl 2 EvolutionaryTrace 1 ExpressionAtlas 1 GO 7 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 2 KEGG 1 MANE-Select 1 MIM 5 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PDB 2 PDBsum 2 PRINTS 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 Reactome 1 RefSeq 1 SIGNOR 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 9311921

Title: NF-AT activation induced by a CAML-interacting member of the tumor necrosis factor receptor superfamily.

PubMed ID: 9311921

DOI: 10.1126/science.278.5335.138

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 10956646

Title: Tumor necrosis factor (TNF) receptor superfamily member TACI is a high affinity receptor for TNF family members APRIL and BLyS.

PubMed ID: 10956646

DOI: 10.1074/jbc.m005224200

PubMed ID: 10973284

Title: APRIL and TALL-I and receptors BCMA and TACI: system for regulating humoral immunity.

PubMed ID: 10973284

DOI: 10.1038/79802

PubMed ID: 10880535

Title: TACI is a TRAF-interacting receptor for TALL-1, a tumor necrosis factor family member involved in B cell regulation.

PubMed ID: 10880535

DOI: 10.1084/jem.192.1.137

PubMed ID: 15542592

Title: Structures of APRIL-receptor complexes: like BCMA, TACI employs only a single cysteine-rich domain for high affinity ligand binding.

PubMed ID: 15542592

DOI: 10.1074/jbc.m411714200

PubMed ID: 16007086

Title: TACI is mutant in common variable immunodeficiency and IgA deficiency.

PubMed ID: 16007086

DOI: 10.1038/ng1601

PubMed ID: 21248752

Title: Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma.

PubMed ID: 21248752

DOI: 10.1038/nature09639

Sequence Information:

  • Length: 293
  • Mass: 31816
  • Checksum: 411799F3DE17A5EB
  • Sequence:
    • MSGLGRSRRG GRSRVDQEER FPQGLWTGVA MRSCPEEQYW DPLLGTCMSC KTICNHQSQR 
TCAAFCRSLS CRKEQGKFYD HLLRDCISCA SICGQHPKQC AYFCENKLRS PVNLPPELRR 
QRSGEVENNS DNSGRYQGLE HRGSEASPAL PGLKLSADQV ALVYSTLGLC LCAVLCCFLV 
AVACFLKKRG DPCSCQPRSR PRQSPAKSSQ DHAMEAGSPV STSPEPVETC SFCFPECRAP 
TQESAVTPGT PDPTCAGRWG CHTRTTVLQP CPHIPDSGLG IVCVPAQEGG PGA