PuSH - Publikationsserver des Helmholtz Zentrums München

Fichtner, M.L.* ; Rübsamen, H.* ; Smolle, M.* ; Schaller, J.* ; Feederle, R. ; Bültmann, A.* ; Kümpfel, T.* ; Schneider, P.* ; Thaler, F.S.* ; Meinl, E.*

Features of isoforms of human soluble TACI.

J. Immunol. 211, 199-208 (2023)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
The BAFF/APRIL-system with the two cytokines BAFF and APRIL and their three receptors, transmembrane activator and CAML interactor (TACI), BAFF receptor, and B-cell maturation Ag, is important for B cell maintenance. The BAFF/APRIL system is a therapeutic target in B cell-derived malignancies and autoimmune diseases. However, unexpected outcomes of clinical trials with atacicept (TACI-Fc) underline our incomplete understanding of this system. Shedding of the three receptors is one important regulatory element. In humans, TACI exists in two isoforms generated through alternative splicing in their extracellular portion: TACI-long (l) has two cysteine-rich domains, whereas TACI-short (s) lacks the first low-affinity one. In this study, we discriminated soluble (s) forms of TACI-l and TACI-s with newly generated mAbs and found that both were spontaneously released from activated human B cells, with a predominance of sTACI-l. Furthermore, sTACI-l was also the dominant isoform in human serum. Vaccination with the mRNA vaccine from BioNTech does not significantly affect the serum levels of sTACI-l. Both TACI-s and TACI-l were shed by a disintegrin and metalloproteinase domain-containing protein 10. TACI-l and TACI-s formed homo- and hetero-oligomers in soluble and membrane-bound forms. Both sTACI-l and sTACI-s acted as decoy receptors for BAFF, but only sTACI-l also efficiently inhibited APRIL. Dimerization of sTACI-l enhanced its decoy functions only slightly. Together, we extend our knowledge of the complexity of the BAFF/APRIL system by identifying and characterizing the two soluble isoforms of TACI.
Altmetric
Weitere Metriken?
[➜Einloggen]
Zusatzinfos bearbeiten [➜Einloggen]
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Common Variable Immunodeficiency; Crystal-structure; Receptor; April; Baff; Bcma; Immunoregulator; Therapy; Antigen; System
ISSN (print) / ISBN 0022-1767
e-ISSN 1550-6606
Zeitschrift Journal of Immunology
Quellenangaben Band: 211, Heft: 2, Seiten: 199-208 Artikelnummer: , Supplement: ,
Verlag American Association of Immunologists
Verlagsort 9650 Rockville Pike, Bethesda, Md 20814 Usa
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) CF Monoclonal Antibodies (CF-MAB)
Förderungen Deutsche Forschungsgemeinschaft research fellowship
Swiss National Science Foundation
Munich Cluster for Systems Neurology (SyNergy)
Else-Kroner Fresenius Stiftung
Gemeinnutzige Hertie Stiftung
Novartis Pharma
Merck
Deutsche Forschungsgemeinschaft