TACI, unlike BAFF-R, is solely activated by oligomeric BAFF and APRIL to support survival of activated B cells and plasmablasts
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.
|Authors||Bossen, C.;Cachero, T. G.;Tardivel, A.;Ingold, K.;Willen, L.;Dobles, M.;Scott, M. L.;Maquelin, A.;Belnoue, E.;Siegrist, C. A.;Chevrier, S.;Acha-Orbea, H.;Leung, H.;Mackay, F.;Tschopp, J.;Schneider, P. :|
|Published Date||2008-01-01 00:00:00|
|OpenAccess Link||https://publications.gimr.garvan.org.au/download.php?2320_10133/08 Bossen Blood.pdf|