Selective activation of TACI by syndecan-2

Bischof, Daniela; Elsawa, Sherine F.; Mantchev, George T.; Yoon, Jeong‐Won; Michels, Grace E.; Nilson, Allan E.; Sutor, Shari L.; Platt, Jeffrey L.; Ansell, Stephen M.; Bulow, Gotz von; Bram, Richard J.

doi:10.1182/blood-2005-01-0256

Cited by 67 publications

(61 citation statements)

References 64 publications

(62 reference statements)

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“…TACI signals triggered with anti-TACI antibodies or with natural ligands may be different, for example, because of a differential impact on TACIproteoglycan interactions, which appear to modulate TACI signals. 45,46 In addition, it has not been demonstrated in vivo that TACI directly transmits negative signals within B cells: B cell hyperplasia in TACI Ϫ/Ϫ mice may also result from the loss of a BAFF/APRIL inhibitor such as a soluble, decoy form of TACI. TACI can indeed be processed at Arg 122 , Arg 110 , and Lys 108 , and each of these cleavage events is predicted to release functional forms of soluble human and mouse TACI.…”

Section: Discussionmentioning

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

263

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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Section: Discussionmentioning

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

263

270

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show abstract

“…[36][37][38] A recent study also demonstrated that syndecans, including syndecan-1, directly bind to tumor cells and activate TACI signaling. 39 These studies may suggest that in contrast to BAFF, APRIL plays a nonredundant role in the survival of myeloma due to its interaction with syndecan-1 and possibly other HSPGs.…”

Section: Antimyeloma Response Of Atacicept and Baffr-ig In Scid-hu Micementioning

confidence: 99%

Atacicept (TACI-Ig) inhibits growth of TACIhigh primary myeloma cells in SCID-hu mice and in coculture with osteoclasts

Yaccoby

Pennisi

et al. 2007

Leukemia

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APRIL (a proliferation-inducing Ligand) and BLyS/BAFF (B-lymphocyte stimulator/B-cell-activating factor of the TNF (tumor necrosis factor) family have been shown to be the survival factors for certain myeloma cells in vitro. BAFF binds to the TNF-related receptors such as B-cell maturation antigen (BCMA), transmembrane activator and CAML interactor (TACI) and BAFFR, whereas APRIL binds to TACI and BCMA and to heparan sulfate proteoglycans (HSPG) such as syndecan-1. TACI gene expression in myeloma reportedly can distinguish tumors with a signature of microenvironment dependence (TACI high ) versus a plasmablastic signature (TACI low ). We tested the effect of atacicept (formerly TACI-Ig, which blocks APRIL and BAFF) and BAFFR-Ig (which blocks BAFF only) on primary myeloma growth in the SCID-hu model and in coculture with osteoclasts. With only few exceptions, atacicept and to a lesser extent BAFFR-Ig, inhibited growth of TACI high but not TACI low myeloma samples in vivo and ex vivo, and the response rate was inversely correlated with TACI expression. Most TACI high myeloma cells were molecularly classified as being low risk with our recently described 70-gene model. APRIL and BAFF were highly expressed by osteoclasts and were upregulated in myeloma cells after coculture with osteoclasts. Our findings suggest that APRIL plays an essential role in the survival of TACI high bone marrow-dependent myeloma cells and TACI gene expression may be a useful predictive marker for patients who could benefit from atacicept treatment.

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“…In addition, APRIL binds to heparan sulfate proteoglycans, which appear to play a predominantly structural role by enabling APRIL cross-linking (13,14), although a distinct signaling role in different contexts cannot be eliminated. In addition to APRIL, TACI can also bind to heparan sulfate proteoglycans, which is suggested to lead to its activation (15). All of these potential binding partners make it difficult to unravel APRIL signaling in a given context and to assess the individual contributions of TACI and BCMA.…”

mentioning

confidence: 99%

The Design and Characterization of Receptor-selective APRIL Variants

Kimberley¹,

Sloot

Guadagnoli³

et al. 2012

Journal of Biological Chemistry

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Background: APRIL binds two receptors, BCMA and TACI, so separating signaling outcomes is difficult. Results: We used an algorithm to design a variant of APRIL that specifically binds BCMA and two variants that selectively bind TACI. Conclusion: TACI and BCMA signals differ in the context of B cell stimulation. Significance: These variants will help decipher APRIL signaling in physiology and disease settings.

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Selective activation of TACI by syndecan-2

Cited by 67 publications

References 64 publications

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

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

Atacicept (TACI-Ig) inhibits growth of TACIhigh primary myeloma cells in SCID-hu mice and in coculture with osteoclasts

The Design and Characterization of Receptor-selective APRIL Variants

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