BLyS receptor signatures resolve homeostatically independent compartments among naïve and antigen-experienced B cells

Treml, Laura S.; Crowley, Jenni E.; Cancro, Michael P.

doi:10.1016/j.smim.2006.07.001

Cited by 42 publications

(37 citation statements)

References 108 publications

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“…3 We here propose an entirely novel concept: perhaps placental BAFF and APRIL are used to drive placental cell maturation, development, and/or differentiation. As summarized recently by Treml et al, 18 BAFF signaling through the BAFF-R regulates the primary B-cell pool, whereas BAFF and/or APRIL acting via the TACI receptor affect short-lived, proliferating B cells The same two cytokines signaling through the BCMA receptor govern memory B cells. The possibility that BAFF in the placenta may have similar actions, at least as regards placental macrophages, is supported by a recent study showing that monocytes exposed to BAFF respond with increased survival, activation, and differentiation.…”

Section: Discussionmentioning

confidence: 92%

“…One microgram of the DNase-treated RNA was reverse-transcribed in a 40-l reaction using 400 U of Moloney-murine leukemia virus reverse transcriptase. The reaction contained 10 mmol/L dithiothreitol, 50 mmol/L Tris-HCl, pH 8.3, 75 mmol/L KCl, 3 mmol/L MgCl 2 , 0.5 mmol/L each of dGTP, dATP, dTTP, and dCTP, 1 g of oligo(dT) [12][13][14][15][16][17][18] and 1 U of RNaseOUT (all from Invitrogen). Reverse transcription was performed using a GeneAmp PCR System 2400 Thermocycler (PerkinElmer Corp., Norwalk, CT) for 1 hour at 37°C, 15 minutes at 70°C, and then chilled on ice.…”

Section: Reverse Transcriptase (Rt)-pcrmentioning

confidence: 99%

“…Regarding TACI, binding to this receptor in mice results in negative regulation of B-lymphocyte proliferation stim-ulated by BAFF, but this seems not to be the case in humans, since patients with TACI mutations have normal numbers of B lymphocytes. 14 Treml et al 18 have commented that TACI has its major impact on short-lived, proliferating B cells. In contrast to BAFF-R and TACI, BCMA is involved in late stages of B cell maturation, being important to the survival of plasmablasts and longlived plasma cells in the bone marrow.…”

mentioning

confidence: 99%

“…In contrast to BAFF-R and TACI, BCMA is involved in late stages of B cell maturation, being important to the survival of plasmablasts and longlived plasma cells in the bone marrow. 13,14,18,20 An early study from our laboratory identified BAFF and APRIL messages and proteins in human placentas. 3 Until recently, when Chang et al 21 reported human monocyte binding of BAFF, B lymphocytes were the only described targets of these two cytokines.…”

mentioning

confidence: 99%

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Signaling Pathways for B Cell-Activating Factor (BAFF) and a Proliferation-Inducing Ligand (APRIL) in Human Placenta

Langat

Wheaton

Platt

et al. 2008

The American Journal of Pathology

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The tumor necrosis superfamily (TNFSF) contains two soluble ligands that are involved in B lymphocyte development, BAFF (B cell activating factor, BlyS, TALL-1, CD257, TNFSF13B) and APRIL (a proliferation inducing ligand, CD256, TNFSF13). These two ligands signal through three receptors: the exclusive BAFF receptor (BAFF-R, CD268, TNFRSF17) and two receptors that recognize both BAFF and APRIL, TACI (transmembraneactivator-1 and calcium-modulator-and cyclophilin ligand-interactor CD267, TNFRSF13B) and BCMA (B cell maturation antigen, CD269, TNFRSF13C). All but BAFF-R are known to be synthesized in term placentas. In this study, expression of the ligands and receptors were distinguished in two embryologically discrete subpopulations of placental cells, villous cytotrophoblast (vCTB) cells and mesenchymal cells (MCs). Real-Time PCR showed that vCTB cells contain low levels of BAFF and APRIL transcripts whereas MCs contain high levels. Both Real-Time PCR and immunohistochemistry identified BAFF-R and BCMA mRNA and proteins in vCTB cells but essentially no TACI. By contrast, MCs contained readily detectable levels of all three receptors. These results illustrating potential autocrine and paracrine pathways for BAFF and APRIL signaling in human placentas suggest that lineage-specific regulation of placental cell viability, differentiation and/or other activities may be novel functions of these proteins. (Am J Pathol

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Section: Discussionmentioning

confidence: 92%

Section: Reverse Transcriptase (Rt)-pcrmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Signaling Pathways for B Cell-Activating Factor (BAFF) and a Proliferation-Inducing Ligand (APRIL) in Human Placenta

Langat

Wheaton

Platt

et al. 2008

The American Journal of Pathology

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“…[1][2][3] BAFF is expressed by myeloid cells and by unidentified radiation-resistant cells, possibly stromal cells of secondary lymphoid organs. [4][5][6] BAFF is either expressed at the cell surface or released into a soluble form through cleavage by an uncharacterized furin.…”

Section: Introductionmentioning

confidence: 99%

TACI, unlike BAFF-R, is solely activated by oligomeric BAFF and APRIL to support survival of activated B cells and plasmablasts

Bossen

Cachero

Tardivel

et al. 2008

Blood

265

270

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The cytokine BAFF binds to the receptors TACI, BCMA, and BAFF-R on B cells, whereas APRIL binds to TACI and BCMA only. The signaling properties of soluble trimeric BAFF (BAFF 3-mer) were compared with those of higher-order BAFF oligomers. All forms of BAFF bound BAFF-R and TACI, and elicited BAFF-R-dependent signals in primary B cells. In contrast, signaling through TACI in mature B cells or plasmablasts was only achieved by higher-order BAFF and APRIL oligomers, all of which were also po-tent activators of a multimerization-dependent reporter signaling pathway. These results indicate that, although BAFF-R and TACI can provide B cells with similar signals, only BAFF-R, but not TACI, can respond to soluble BAFF 3-mer, which is the main form of BAFF found in circulation. BAFF 60-mer, an efficient TACI agonist, was also detected in plasma of BAFF transgenic and nontransgenic mice and was more than 100-fold more active than BAFF 3-mer for the activation of multimerization-dependent signals. TACI supported survival of activated B cells and plasmablasts in vitro, providing a rational basis to explain the immunoglobulin deficiency reported in TACI-deficient persons

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Effect of long‐term belimumab treatment on b cells in systemic lupus erythematosus: Extension of a phase II, double‐blind, placebo‐controlled, dose‐ranging study

Jacobi¹,

Huang²,

Wang³

et al. 2009

Arthritis & Rheumatism

206

145

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Objective. To understand the effects of long-term BLyS inhibition in human systemic lupus erythematosus (SLE).Methods. Seventeen patients with SLE who were enrolled in a clinical trial of belimumab, a BLyS-specific inhibitor, plus standard of care therapy were studied. Phenotypic analysis of lymphocytes was performed using flow cytometry. Circulating antibody-secreting cells were enumerated using enzyme-linked immunospot assay. Serum was analyzed by enzyme-linked immunosorbent assay using an antibody that recognizes products of the V H 4-34 gene. Lymphocyte counts, Ig levels, and anti-double-stranded DNA antibody levels were available as part of the clinical trial analyses.Results. Samples were collected on days 0, 84, 168, 365, and 532 and after day 730. The total number of B cells started to decrease from baseline between days 84 and 168. This was due to a decrease in naive and transitional B cells. CD27؉IgD؉ memory B cells and plasmablasts decreased only after 532 days, whereas CD27؉IgD؊ memory B cells were not affected, and there were no changes in T cells. Serum IgM levels began to decline between days 84 and 168, but there were no changes in serum levels of IgG, IgG anti-DNA antibodies, or V H 4-34 antibodies during the study. SLE patients had more IgM-, IgG-, and autoantibodyproducing B cells than did normal controls on day 0. There was only a modest decrease in the frequency of total IgM-producing, but not IgG-producing, cells on days 365 and 532, consistent with the phenotypic and serologic data.Conclusion. Our data confirm the dependence of newly formed B cells on BLyS for survival in humans. In contrast, memory B cells and plasma cells are less susceptible to selective BLyS inhibition.

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BLyS receptor signatures resolve homeostatically independent compartments among naïve and antigen-experienced B cells

Cited by 42 publications

References 108 publications

Signaling Pathways for B Cell-Activating Factor (BAFF) and a Proliferation-Inducing Ligand (APRIL) in Human Placenta

Signaling Pathways for B Cell-Activating Factor (BAFF) and a Proliferation-Inducing Ligand (APRIL) in Human Placenta

TACI, unlike BAFF-R, is solely activated by oligomeric BAFF and APRIL to support survival of activated B cells and plasmablasts

Effect of long‐term belimumab treatment on b cells in systemic lupus erythematosus: Extension of a phase II, double‐blind, placebo‐controlled, dose‐ranging study

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