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Title

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

Authors
Bossen, Claudia
Cachero, Teresa G.
Tardivel, Aubry
Ingold, Karine
Willen, Laure
Dobles, Max
Scott, Martin L.
Maquelin, Aris
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Published in Blood. 2008, vol. 111, no. 3, p. 1004-12
Abstract 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.
Keywords Amino Acid SequenceAnimalsAntibodies/immunologyAntibody Formation/immunologyB-Cell Activating Factor/chemistry/genetics/metabolismB-Cell Activation Factor Receptor/immunology/metabolismB-Lymphocytes/cytology/immunology/metabolismCell LineCell ProliferationHistocompatibility Antigens Class II/immunologyHumansImmunoglobulins/biosynthesis/immunologyLigandsLymphocyte ActivationMiceMice, KnockoutMice, TransgenicMolecular Sequence DataSequence AlignmentSignal TransductionSpleen/immunologyTransmembrane Activator and CAML Interactor Protein/deficiency/genetics/metabolismTumor Necrosis Factor Ligand Superfamily Member 13/genetics/metabolismUp-Regulation
Identifiers
PMID: 17942754
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Other version: http://bloodjournal.hematologylibrary.org/cgi/content/full/111/3/1004
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Research group Centre de Vaccinologie et d'Immunologie néonatale (177)
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BOSSEN, Claudia et al. TACI, unlike BAFF-R, is solely activated by oligomeric BAFF and APRIL to support survival of activated B cells and plasmablasts. In: Blood, 2008, vol. 111, n° 3, p. 1004-12. https://archive-ouverte.unige.ch/unige:2527

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Deposited on : 2009-08-27

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