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

. 2008 Feb 1;111(3):1004-12.

doi: 10.1182/blood-2007-09-110874. Epub 2007 Oct 17.

Teresa G Cachero, Aubry Tardivel, Karine Ingold, Laure Willen, Max Dobles, Martin L Scott, Aris Maquelin, Elodie Belnoue, Claire-Anne Siegrist, Stéphane Chevrier, Hans Acha-Orbea, Helen Leung, Fabienne Mackay, Jürg Tschopp, Pascal Schneider

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

Claudia Bossen et al. Blood. 2008.

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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.

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