BAFF-R, a Newly Identified TNF Receptor That Specifically Interacts with BAFF

Thompson, Jeffrey S.; Bixler, Sarah A.; Qian, Fang; Vora, Kalpit A.; Scott, Martin; Cachero, Teresa G.; Hession, Catherine; Schneider, Pascal; Sizing, Irene; Mullen, Colleen; Strauch, Kathy; Zafari, Mohammad; Benjamin, Christopher D.; Tschopp, Jürg; Browning, Jeffrey L.; Ambrose, Christine

doi:10.1126/science.1061965

Cited by 824 publications

(727 citation statements)

References 29 publications

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“…Such a receptor known as BAFF-R or BR3 (BLyS receptor 3) was indeed identified by an expression-cloning strategy. 94,95 Unlike TACI and BCMA, BR3 is specific only for BAFF. BAFF-R has also been shown to be specifically disrupted by a spontaneously insertional event in the A/WySnJ mouse strain, which lacks peripheral B-cells, that results in the truncation of the receptor and the deletion of the last eight amino acids of the intracellular domain of the receptor.…”

Section: Tnf Family Members In B-cell Developmentmentioning

confidence: 99%

“…BAFF-R has also been shown to be specifically disrupted by a spontaneously insertional event in the A/WySnJ mouse strain, which lacks peripheral B-cells, that results in the truncation of the receptor and the deletion of the last eight amino acids of the intracellular domain of the receptor. 94,95 It should be noted that A/WySnJ mice have more B-cells than mice deficient for BAFF, indicating that the BAFF-R allele in the A/WySnJ mice may represent a partial loss of function of the receptor. These data suggest that BAFF-R is the critical mediator of B-cell survival by BAFF.…”

Section: Tnf Family Members In B-cell Developmentmentioning

confidence: 99%

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Apoptosis in the development of the immune system

Opferman

2007

Cell Death Differ

121

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Apoptosis is a conserved genetic program critical for the development and homeostasis of the immune system. During the early stages of lymphopoiesis, growth factor signaling is an essential regulator of homeostasis by regulating the survival of lymphocyte progenitors. During differentiation, apoptosis ensures that lymphocytes express functional antigen receptors and is essential for eliminating lymphocytes with dangerous self-reactive specificities. Many of these critical cell death checkpoints during immune development are regulated by the BCL-2 family of proteins, which is comprised of both pro-and antiapoptotic members, and members of the tumor necrosis factor death receptor family. Aberrations in the expression or function of these cell death modulators can result in pathological conditions including immune deficiency, autoimmunity, and cancer. This review will describe how apoptosis regulates these critical control points during immune development.

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Section: Tnf Family Members In B-cell Developmentmentioning

confidence: 99%

Section: Tnf Family Members In B-cell Developmentmentioning

confidence: 99%

Apoptosis in the development of the immune system

Opferman

2007

Cell Death Differ

121

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“…BAFF (also known as BlyS, TALL-1, zTNF4, THANK, and TNFSF 13B) has emerged as a critical regulator of B cell survival and maturation in the periphery. Mice deficient in BAFF display severe loss of mature B cells and attenuated antibody responses [8][9][10][11][12][13][14]. The interaction between CD40 and its ligand CD40L is required for T cell-dependent B cell activation and antibody production [10,15].…”

Section: Introductionmentioning

confidence: 99%

Deficiency of Act1, a critical modulator of B cell function, leads to development of Sjögren's syndrome

et al. 2008

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CD40L and B lymphocyte‐activating factor (BAFF), members of the TNF superfamily, play critical roles in B cell survival and activation, and in the regulation of humoral immunity. We previously reported that the adaptor molecule Act1 functions as a negative regulator of CD40‐ and BAFF‐mediated B cell survival. Here we demonstrated that mice deficient in Act1 developed systemic autoimmune disease with histological and serological features of human Sjögren's syndrome (SS), in association with systemic lupus erythematosus‐like nephritis. Analyses of Act1−/−CD40−/− and Act1−/−BAFF−/− double‐deficient mice revealed that Act1 regulates different stages of the disease development through its impact on both CD40‐ and BAFF‐mediated pathways. We found that Act1 modulates the survival of autoreactive B cells mainly through its negative regulatory role in BAFF‐mediated cell survival, while the effect of Act1 on autoantibody production is likely through modulation of CD40‐mediated T cell‐dependent antibody response. The impact of Act1 on both BAFF and CD40 pathways establishes Act1‐deficient mice as a unique model to study distinct steps of autoimmunity and regulation of self tolerance.

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“…18,19 Recently, another receptor for BLyS, BAFF-R (also called BR3) was identified, which does not bind to APRIL. 20,21 Several lines of evidence indicate that these receptorligand systems crucially contribute to the pathogenesis of the autoimmune diseases. Transgenic mice overexpressing BLyS develop symptoms characteristic of systemic lupus erythematosus (SLE).…”

Section: Introductionmentioning

confidence: 99%

Analysis on the association of human BLYS (BAFF, TNFSF13B) polymorphisms with systemic lupus erythematosus and rheumatoid arthritis

et al. 2002

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Recent studies indicated a substantial role of BLyS (BAFF, TNFSF13B) in the pathogenesis of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in humans and in animal models. This study was conducted to screen for polymorphisms of human BLYS, and to examine whether they are involved in the genetic susceptibility to human SLE and RA. A systematic polymorphism screening was performed in the coding region, 5 0 and 3 0 untranslated regions, and promoter region of human BLYS. Association of the detected polymorphisms with SLE and RA was analyzed in 221 Japanese patients with RA, 156 with SLE, and 227 healthy individuals, using the case-control approach. Four single nucleotide polymorphisms (SNPs) in the promoter, one SNP in intron 1, and one rare nonsynonymous substitution (Ala105Thr) in the coding region were detected. The BLYS SNPs were found to form three common haplotypes. Significant association with the susceptibility to SLE or RA was not observed. However, a tendency for the increase of À871T/T genotype was observed in SLE patients with anti-Sm antibody (P ¼ 0.082). BLYS mRNA level was significantly elevated in the monocytes from individuals carrying À871T (P ¼ 0.010). In addition, although statistically not significant, 105Thr allele was slightly increased in patients with RA compared with controls (P ¼ 0.058). Characterizing the functional and clinical significance of these new SNPs requires further study.

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BAFF-R, a Newly Identified TNF Receptor That Specifically Interacts with BAFF

Cited by 824 publications

References 29 publications

Apoptosis in the development of the immune system

Apoptosis in the development of the immune system

Deficiency of Act1, a critical modulator of B cell function, leads to development of Sjögren's syndrome

Analysis on the association of human BLYS (BAFF, TNFSF13B) polymorphisms with systemic lupus erythematosus and rheumatoid arthritis

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