Disease relevance of TNFRSF17

• TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease [1].
• A new gene, BCM, on chromosome 16 is fused to the interleukin 2 gene by a t(4;16)(q26;p13) translocation in a malignant T cell lymphoma [2].
• Moreover, BAFF (0-100 ng/mL) increases adhesion of multiple myeloma lines to BMSCs in a dose-dependent manner; conversely, transmembrane activator and calcium modulator and cyclophylin ligand interactor-Ig or B-cell maturation antigen/Fc blocked BAFF stimulation [3].
• B cell maturation in chronic lymphocytic leukemia. III. Effect of recombinant cytokines on leukemic B cell proliferation [4].
• The Th1 cytokine IFN-gamma is important in inducing B-cell maturation and in helping anti-AChR antibody production and, thereby, for induction of clinical signs and symptoms [5].

Psychiatry related information on TNFRSF17

• BACKGROUND: Body cell mass (BCM) may be estimated in clinical practice to assess functional nutritional status, eg, in patients with anorexia nervosa [6].
• The average time spent weekly doing physical activity resulted in T1DM group directly correlated to BCM (P < 0.001) and inversely correlated with BMDspine (P < 0.05) and L2L4BMDvol (P < 0.01) [7].
• The objectives of this observational study were as follows: 1) to compare minimal observable energy expenditure (MOEE) between 2 subgroups of breast-fed infants, a BM group in which breast milk was the only source of milk and a BCM group given cow's milk in addition to breast milk; and 2) to identify potential mediators of a feeding pattern effect [8].

High impact information on TNFRSF17

• Thus, the precursor cells that monoclonally expand to produce a lymphoid crisis are capable of immunoglobulin-gene rearrangements and represent discrete steps in early B-cell maturation [9].
• Here we determine the crystal structures of sTALL-1 complexed with the extracellular domains of BCMA and BAFF-R at 2.6 and 2.5 A, respectively [10].
• Depletion of circulating immunoglobulins or of individual Fc-gamma receptors had no effect on scrapie pathogenesis if B-cell maturation was unaffected [11].
• In vivo, ICOS is highly expressed on tonsillar T cells, which are closely associated with B cells in the apical light zone of germinal centres, the site of terminal B-cell maturation [12].
• Signalling by membrane immunoglobulin, the B-lymphocyte antigen receptor, regulates B-cell maturation and activation [13].

Chemical compound and disease context of TNFRSF17

• PURPOSE: To compare the sensitivity and specificity of an automated microparticle enzyme immunoassay (MEIA) for breast cancer mucin (IMx BCM; Abbott Laboratories, North Chicago, IL) to that of CA15-3 and carcinoembryonic antigen (CEA) for detecting and monitoring breast cancer [14].
• Comparison of these results with published data for young adults indicates that obligatory urinary N losses in elderly women are similar to those for young women when expressed per unit body weight but higher than young women and men when expressed per unit creatinine excretion and per unit BCM [15].
• Dronabinol and megestrol acetate may promote weight gain; however, dronabinol may have adverse effects, and most of the gain with megestrol acetate is in fat rather than BCM [16].
• AIMS: To verify whether fluorouracil (FU) clearance (CL) and volume of distribution (V(ss)) are better correlated with specific body compartments, such as body cell mass (BCM), total body water (TBW) or fat free mass (FFM), rather than with body surface area (BSA) or total body weight (BW) [17].
• We used a sensitive whole body counter which measures potassium-40 (40K) to determine total body potassium and to estimate body cell mass (BCM) in 104 previously untreated patients with upper gastrointestinal malignancies, 233 normal volunteers, and 18 patients with anorexia nervosa [18].

Biological context of TNFRSF17

• APRIL and TALL-I and receptors BCMA and TACI: system for regulating humoral immunity [19].
• In contrast, mice transgenic for a soluble form of BCMA, which binds APRIL, have no detectable B cell phenotype [20].
• Incorporation of the Q25D and R27Y substitutions into BCMA produced a dual specificity variant, since it has comparable binding affinity for both APRIL and BAFF, IC50 = 350 and 700 nm, respectively [21].
• These results suggest that APRIL is the preferred ligand for BCMA and show that specificity can be further modified through amino acid substitutions [21].
• Presence of four major haplotypes in human BCMA gene: lack of association with systemic lupus erythematosus and rheumatoid arthritis [22].

Anatomical context of TNFRSF17

• Thus, APRIL-TALL-I and BCMA-TACI form a two ligands-two receptors pathway involved in stimulation of B and T cell function [19].
• Previously, we reported in a human malignant myeloma cell line that BCMA is not primarily present on the cell surface but lies in a perinuclear structure that partially overlaps the Golgi apparatus [23].
• BAFF-R expression increased initially and then decreased with a corresponding induction of TACI and BCMA expression during differentiation to plasma cells (PCs) [24].
• However, GCs in B cell maturation Ag-Fc-treated mice dissipated more rapidly than those of control mice and did not form a mature follicular dendritic cell reticulum [25].
• Unlike their putative germinal center B-cell precursors, HRS cells lacked BAFF-R, but expressed TACI and BCMA, a phenotype similar to that of plasmacytoid B cells [26].

Associations of TNFRSF17 with chemical compounds

• Second, shotgun alanine scanning of BCMA was used to map critical residues for either APRIL or BAFF binding [21].
• The single cysteine-rich domain of BCMA and BAFF-R both have saddle-like architectures, which sit on the horseback-like surface formed by four coil regions on each individual sTALL-1 monomer [10].
• In agreement, mutation of three lysines in a putative heparin sulfate-binding motif, which is not part of the TNF fold, destroys interaction with HSPG, while binding to BCMA is unaffected [27].
• Regulation of B cell maturation and differentiation. I. Suppression of pokeweed mitogen-induced B cell differentiation by tumor necrosis factor (TNF) [28].
• Moreover, PGE2(+) T lymphocytes did exert a strong suppressor activity on mitogen- or allogeneic cell-induced lymphocyte proliferation as well as on pokeweed mitogen-driven B cell maturation into Ig-containing cells [29].

Physical interactions of TNFRSF17

• A soluble receptor containing the extracellular domain of BCMA blocks the binding of TALL-1 to its receptor on the plasma membrane and inhibits TALL-1-triggered B lymphocyte costimulation [30].
• APRIL binds BCMA with higher affinity than TACI [31].

Regulatory relationships of TNFRSF17

• The identification of BCMA as a NF-kappaB-activating receptor for TALL-1 suggests molecular targets for drug development against certain immunodeficient or autoimmune diseases [30].
• This is the first identification of ligands that selectively activate TACI without simultaneously triggering BCMA or BAFF-R [32].
• Potential role of CARMA1 in CD40-induced splenic B cell proliferation and marginal zone B cell maturation [33].
• This differential effect of "low" and "high" concentrations of IL 6 on activated B cells may solve controversy on the role of IL 6 as an early or late agent in B cell maturation [34].
• Altogether, these results indicate that CPP32 is preferentially expressed in germinal centers and thus could be involved in B-cell maturation [35].

Other interactions of TNFRSF17

• Overexpression of BCMA activates NF-kappaB, and this activation is potentiated by TALL-1 [30].
• Three of these new CDs, CD267, CD269, and CD307 presented a B cell-restricted expression pattern [36].
• Engineering an APRIL-specific B cell maturation antigen [21].
• The interaction of CD40L on T-cells and its receptor CD40 on B-cells is essential for lymphocyte signalling leading to immunoglobulin class switching and B-cell maturation [37].
• IL-15 induces T cell proliferation, B cell maturation and natural killer (NK) cell cytotoxicity, and is a chemoattractant for T cells [38].

Analytical, diagnostic and therapeutic context of TNFRSF17

• Confocal scanning laser microscopy of U266 plasma cells labeled with markers of various Golgi apparatus subcompartments strongly suggests that BCMAp is located in the cis part of the Golgi apparatus [39].
• Polyclonal antibodies were used to show, by cellular fractionation and immunoprecipitation, that BCMAp is a non-glycosylated integral membrane protein [39].
• Monoclonal antibodies reactive with B cell-specific differentiation and other antigens were used to investigate stages of B cell maturation in human lymphoid tissue, using an immunoperoxidase technique on frozen tissue sections [40].
• Sequence analysis of the immunoglobulin heavy chain complementarity determining region (CDR)-III of B-lineage cells at various stages has provided important insights concerning B cell maturation and selection [41].
• Immunophenotyping with a panel of markers suggested that the lines derived from cells that had undergone transformation at distinct stages of B-cell maturation [42].

References