BLyS: Member of the Tumor Necrosis Factor Family and B Lymphocyte Stimulator

Moore, Paul A.; Belvedere, Ornella; Orr, A. S.; Pieri, Krystyna; LaFleur, David W.; Feng, Ping; Soppet, Daniel; Charters, Meghan; Gentz, Reiner; Parmelee, David C.; Li, Yuling; Galperina, Olga; Giri, Judith G.; Roschke, Viktor; Nardelli, Bernardetta; Carrell, Jeffrey A.; Sosnovtseva, Svetlana; Greenfield, Wilbert; Ruben, Steven M.; Olsen, Henrik S.; Fikes, James; Hilbert, David M.

doi:10.1126/science.285.5425.260

Cited by 1,045 publications

(950 citation statements)

References 27 publications

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“…Initial descriptions of BAFF revealed profound positive effects on mature B cells both in vivo and in vitro [18,19]. The subsequent discovery of BAFFr, a B-lineage restricted receptor whose sole natural ligand is BAFF, showed that BAFF-BAFFr interactions were crucial to maintaining normal peripheral B cell numbers [20,21].…”

Section: Baff/baffr Signaling Integrates Primary B Cell Selection Andmentioning

confidence: 99%

BAFF and the plasticity of peripheral B cell tolerance

Stadanlick

Cancro

2008

Current Opinion in Immunology

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BAFF and its receptors play a crucial role in peripheral B cell selection and survival, by dictating the set point for mature primary B cell numbers and adjusting thresholds for specificity-based selection during transitional differentiation. The notion that selective stringency can be varied on the basis of homeostatic demands reveals a previously unappreciated degree of plasticity in B cell tolerance, and suggests a paradigm that unites peripheral negative and positive selection with the maintenance of mature B cell numbers. Moreover, it implies a developmentally regulated coupling of BCR and BAFF receptors at the transitional stages and beyond.

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Section: Baff/baffr Signaling Integrates Primary B Cell Selection Andmentioning

confidence: 99%

BAFF and the plasticity of peripheral B cell tolerance

Stadanlick

Cancro

2008

Current Opinion in Immunology

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“…BAFF plays an important role in peripheral B-cell survival, a crucial function that has a considerable impact on B-cell maturation, immune responses and the pathogenesis of autoimmune diseases [56]. BAFF can potentiate antibody responses and increase the number of plasma cells [57,58]. In fact, excessive BAFF production seems to be able to subvert B-cell tolerance [59,60].…”

Section: Constructs Expression and Production Of Vlp/gp41 Variantsmentioning

confidence: 99%

Immunogenicity of recombinant human immunodeficiency virus type 1-like particles expressing gp41 derivatives in a pre-fusion state

Kim

Qiao

et al. 2007

Vaccine

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The conserved membrane proximal external region (MPER) of the ectodomain of human immunodeficiency virus type 1 (HIV-1) gp41 is the target of two broadly neutralizing antibodies, 2F5 and 4E10. However, no neutralizing antibodies have been elicited against immunogens bearing these epitopes. Given that structural and biochemical studies suggest that the lipid membrane of the virion is involved in their proper configuration, HIV-1 gp41 derivatives in a pre-fusion state were expressed on the surface of immature virus like particles (VLP) derived from Sf9 cells. Guinea pigs were immunized with three doses of VLPs or Sf9 cells presenting gp41 derivatives with or without E. coli heat-labile enterotoxin (LT) as an adjuvant. While immune sera contained high titer anti-VLP antibodies, the specific anti-gp41 antibody responses were low with no neutralizing antibodies detected. An explanation for this absence may be the low level of gp41 expression relative to the many other proteins derived from host cells which are incorporated onto the VLP surface. In addition, the anti-gp41 immune response was preferentially directed to the C-helical domain, away from the MPER. Future vaccine design needs to contend with the complexity of epitope display as well as immunodominance.

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Section: Introductionmentioning

confidence: 99%

“…[1][2][3][4][5] BLyS is a potent B cell co-stimulator, and promotes B cell differentiation, proliferation and survival. 1,2,[6][7][8][9][10] In BLyS deficient mice, the number of B cells, serum IgG and IgM levels were decreased, and B cell development was blocked at the transitional T1 stage. 11 BLyS and a proliferation-inducing ligand (APRIL) bind to B cell maturation antigen (BCMA) and transmembrane activator and CAML-interactor (TACI), 4,12,13 which belong to the tumor necrosis factor receptor superfamily and are mainly expressed in B cells.…”

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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BLyS: Member of the Tumor Necrosis Factor Family and B Lymphocyte Stimulator

Cited by 1,045 publications

References 27 publications

BAFF and the plasticity of peripheral B cell tolerance

BAFF and the plasticity of peripheral B cell tolerance

Immunogenicity of recombinant human immunodeficiency virus type 1-like particles expressing gp41 derivatives in a pre-fusion state

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

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