Disease relevance of TNFRSF13C

• Expression of BCMA, TACI, and BAFF-R in multiple myeloma: a mechanism for growth and survival [1].
• BAFF-binding determinants were identified by shotgun alanine-scanning mutagenesis of the BR3 ECD expressed on phage [2].
• Coimmunoprecipitation experiments indicated that BAFF-R interacts with TRAF3 in B lymphoma cells and this interaction is stimulated by TALL-1 treatment [3].
• To test this hypothesis, we sequenced the BAFF-R gene in 48 patients with common variable immunodeficiency (CVID) along with 57 healthy controls [4].
• Seventy-seven (78%) of 116 cases of B-cell lymphoproliferative disorders were BAFF-R-positive by immunohistochemical and/or flow cytometric immunophenotypic analysis, including most cases of mantle cell lymphoma, follicular lymphoma, marginal zone lymphoma, chronic lymphocytic leukemia, hairy cell leukemia, and diffuse large B-cell lymphoma [5].

High impact information on TNFRSF13C

• The chromosomes, especially the Balbiani rings (BR2, BR1 and BR3), were examined during periods of stimulated and repressed RNA synthesis [6].
• 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 [7].
• Thus, BAFF-R appears to be the principal receptor for BAFF-mediated mature B cell survival [8].
• Consistent with this, the BAFF-R locus is disrupted in A/WySnJ mice, which display a B cell phenotype qualitatively similar to that of the BAFF-deficient mice [8].
• BAFF was localized in astrocytes close to BAFF-R-expressing immune cells [9].

Chemical compound and disease context of TNFRSF13C

• An analytical strategy combining fractal geometry and grey-level co-occurrence matrix (GLCM) statistics was devised to investigate ultrastructural changes in oestrogen-insensitive SK-BR3 human breast cancer cells undergoing apoptosis in vitro [10].

Biological context of TNFRSF13C

• Outside of the turn, mutagenesis identifies additional hydrophobic contacts that enhance the BAFF-BR3 interaction [2].
• Consistently, blocking of BAFF-R alone with specific mAb inhibited GC-B cell proliferation and PC generation in the early period of their differentiation, whereas depletion of BAFF with TACI-Ig exhibited consistent inhibition throughout the differentiation [11].
• Blocking BR3 did not inhibit the capacity of BAFF to support CLL cell survival in vitro [12].
• Impact of the BAFF/BR3 axis on B cell survival, germinal center maintenance and antibody production [13].
• The differential expression of LCK and BAFF-receptor and their role in apoptosis in human lymphomas [14].

Anatomical context of TNFRSF13C

• BAFF/BAFF-R interactions are critical for B cell regulation, and signaling from this ligand-receptor complex results in NF-kappaB activation [15].
• BAFF was also an effective costimulator for T cells, and this costimulation occurs entirely through BAFF-R [16].
• In reactive lymphoid tissues, BAFF-R is expressed by B cells colonizing the mantle zones, by a subset of cells within germinal centers, and rare cells in the interfollicular T-cell zone [5].
• In hyperplastic thymi, macrophages expressed APRIL and BAFF, and germinal-center B cells, BAFF-R [17].
• After receiving T cell help, the anti-chromatin B cells that have differentiated into short-lived plasma cells no longer express BR3 but retain TACI [18].

Associations of TNFRSF13C with chemical compounds

• However, the extracellular domain (ECD) of BR3 consists of only a partial CRD, with cysteine spacing distinct from other modules described previously [2].
• Alanine scanning and crystallographic structural analysis of the CB3s/BR3 complex reveal that CB3s mimics BAFF by interacting with a similar region of the BR3 surface [19].
• Reaction of vanadocene [V(Cp)2] with "activated" nitrile R1CN.L (L: Lewis acid), obtained by the reaction of borane adducts (L = BR3; R = C6F5, 2,6-F2C6H3, 3,4,5-F3C6H2) with nitriles (CH3CN, F3CC6H4CN), yields the borane adduct of vanada(IV)azirine complexes [V(Cp)2(eta 2-R1C = N.L)] [20].
• SK-BR3 cells entered the early stage of apoptosis within 24 h of treatment with calcimycin, which induced detectable changes in nuclear components, as documented by increased values of most GLCM parameters and by the general reduction of the fractal dimensions [10].
• Mice injected with MDA-231 BR3 into the carotid artery were treated with the VEGF-receptor tyrosine kinase inhibitor PTK787/Z 222584 [21].

Physical interactions of TNFRSF13C

• In this study, we report the crystal structure of a 24-residue fragment of the cytoplasmic portion of BAFF-R bound in complex with TRAF3 [15].
• However, BAFF-R binds only one TRAF adaptor, TRAF3, and this interaction negatively regulates activation of NF-kappaB [15].
• BAFF and APRIL bind to BAFF receptor and TACI and are major B-cell survival factors [22].

Regulatory relationships of TNFRSF13C

• Moreover, overexpression of TRAF3 inhibits BAFF-R-mediated NF-kappaB activation and IL-10 production [3].

Other interactions of TNFRSF13C

• Key molecular contacts promote recognition of the BAFF receptor by TNF receptor-associated factor 3: implications for intracellular signaling regulation [15].
• The recognition motif (162)PVPAT(166) in BAFF-R is accommodated in the same binding crevice on TRAF3 that binds two related TNFRs, CD40 and LTbetaR, but is presented in a completely different structural framework [15].
• In the C-terminal arm, key stabilizing contacts are made, including critical hydrogen bonds with Gln(379) in TRAF3 that define the molecular basis for selective binding of BAFF-R solely to this member of the TRAF family [15].
• The BR3 fold is analogous to the first half of a canonical TNFR CRD but is stabilized by an additional noncanonical disulfide bond [2].
• Expression and occupancy of BAFF-R on B cells in systemic lupus erythematosus [23].

Analytical, diagnostic and therapeutic context of TNFRSF13C

• This effort identified TNFR-associated factor (TRAF)3 as a protein specifically interacting with BAFF-R in yeast two-hybrid assays [3].
• In contrast, cases of precursor B lymphoblastic lymphoma, Burkitt lymphoma, and nodular lymphocyte-predominant Hodgkin lymphoma exhibit weak to negative staining for BAFF-R [5].
• The expression of BAFF receptor (BAFFR) on CD19+ B cells was assessed by flow cytometry [24].
• Further, BcR ligation up-regulates expression of the BLySR B cell maturation defect/BLySR3 (Bcmd/BR3), but not other known BLySRs [25].
• Taken together, these data indicate the BAFF/BAFF-R pathway contributes to both T and B cell responses and may be an attractive target for control of acute and chronic allograft rejection [26].

References