Disease relevance of Tnfrsf13c

• Unexpectedly, the BAFF-R mutation in MRL-lpr mice did not result in decreased autoantibody production, hypergammaglobulinaemia or immune complex-mediated glomerulonephritis [1].
• Further studies found increased numbers of B cells in the bone marrow of BAFF-R-mutant MRL-lpr mice compared to the BAFF-R-intact lupus mice [1].
• By replacing BAFF-R signals, constitutive canonical NF-kappaB signaling, a hallmark of various B cell lymphomas, causes accumulation of resting B cells and promotes their proliferation and survival upon activation, but does not per se induce lymphomagenesis [2].
• Recent studies on BAFF, a member of the tumor necrosis factor family, and the discovery of a new BAFF receptor have revealed that this ligand-receptor pair is essential for B-cell survival and differentiation, holding promise for a better understanding and treatment of some autoimmune diseases and lymphomas [3].
• Several QTLs controlled the mastocytosis in this intercross, and it was not possible to determine whether any of them co-segregated with Bcmd-1 [4].

High impact information on Tnfrsf13c

• In a Perspective, Waldschmidt and Noelle discuss new findings showing that the TNF family ligand BAFF and its receptor BAFF-R are crucial for selecting transitional B cells into the mature B cell pool (Thompson et al., Schiemann et al.) [5].
• In addition, canonical NF-kappaB activity mediates differentiation and proper localization of follicular and marginal zone B cells in the absence of BAFF-R, but not CD19 [2].
• TNF receptor (TNFR) superfamily members, CD40, and BAFFR play critical roles in B cell survival and differentiation [6].
• These findings demonstrate that Act1 plays an important role in the homeostasis of B cells by attenuating CD40 and BAFFR signaling [6].
• Heightened expression of B cell maturation antigen (BCMA), and lowered expression of transmembrane activator and cyclophilin ligand interactor and BAFF receptor in PCs relative to resting B cells suggests a vital role of BCMA in PC survival [7].

Biological context of Tnfrsf13c

• To test this idea, we created lines of mice coexpressing a Bcl-2 transgene and a signaling-deficient form of the BAFF-R derived from the B lymphopenic A/WySnJ strain [8].
• Unexpected development of autoimmunity in BAFF-R-mutant MRL-lpr mice [1].
• Rather, the ability of BAFF-R-mutant lpr splenic B cells to produce immunoglobulins in vitro was not decreased, although germinal centre formation, antibody response and B-cell proliferation were impaired [1].
• Previous genetic mapping placed Bcmd near Srebf2 on chromosome 15 [9].
• Enforced bcl-xL gene expression restored splenic B lymphocyte development in BAFF-R mutant mice [10].

Anatomical context of Tnfrsf13c

• Then, we have examined the question of whether the reduced number of mature B cells in PLC-gamma2-/- mice is caused by a defect in either BCR or BAFF-R signaling [11].
• Normal induction but attenuated progression of germinal center responses in BAFF and BAFF-R signaling-deficient mice [12].
• BAFF also affects T cell function through binding to one of the BAFF receptors, BAFF-R [13].
• ELISPOT analysis revealed that BAFF-R-mutant MRL-lpr mice had more antibody-secreting cells in their bone marrow than the control mice [1].
• The BAFF-R mutation markedly impaired the development of immature, mature and marginal zone B cells in the spleens of MRL-lpr mice [1].

Associations of Tnfrsf13c with chemical compounds

• The Br3 antibody, which specifically recognizes CldUrd, was applied first, followed by indirect staining with goat anti-mouse phycoerythrin [14].

Regulatory relationships of Tnfrsf13c

• These studies clearly demonstrate that BAFF regulates Ab responses in vivo through receptors in addition to BAFF-R [15].
• In addition, we propose that BAFF-R signaling enhances the expression of survival genes through direct chromatin modifications in NF-kappa B target gene promoters [16].

Other interactions of Tnfrsf13c

• A BAFF-specific receptor (BAFF-R; BR3) appears to mediate these functions via activation of the NF-kappaB2 pathway [8].
• Therefore, our data suggest that the BAFF-R-mediated survival signal, provided by PLC-gamma2, is not sufficient to promote B cell maturation, and that, in addition, activation of PLC-gamma2 by BCR is required for B cell development [11].
• This indicates that BASH-mediated BCR signaling primarily controls B cell survival and maturation, with BAFF-R signaling and its inhibition of PKCdelta acting as a secondary regulator [17].
• In addition, Bcmd-2 or a linked locus controls mastocytosis, while Bcmd-1 does not, as indicated by splenic mast cell analysis in the congenic strains [4].
• We have used the CBA/N X-linked B-cell maturation defect (xid) as a probe to analyse the B-cell subset involved in spontaneous anti-DNA production in MRL/1 and NZB mice [18].

Analytical, diagnostic and therapeutic context of Tnfrsf13c

• Three polyclonal antisera recognizing the uncleaved native toxin could be found using an ELISA test (Br3, Bro2, Bro5) [19].

References