Ligand-independent oligomerization of TACI is controlled by the transmembrane domain and regulates proliferation of activated B cells.

Autor:	Smulski CR; Department of Biochemistry, University of Lausanne, Ch. des Boveresses 155, 1066 Epalinges, Switzerland; Faculty of Medicine and Medical Center, University of Freiburg, Department of Rheumatology and Center for Chronic Immunodeficiency, Breisacherstr. 115, 79106 Freiburg, Germany; Medical Physics Department, Centro Atómico Bariloche, Comisión Nacional de Energía Atómica (CNEA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Avenida E- Bustillo 9500, R8402AGP Río Negro, San Carlos de Bariloche, Argentina. Electronic address: cristian.smulski@cab.cnea.gov.ar., Zhang L; Faculty of Medicine and Medical Center, University of Freiburg, Department of Rheumatology and Center for Chronic Immunodeficiency, Breisacherstr. 115, 79106 Freiburg, Germany., Burek M; Faculty of Medicine and Medical Center, University of Freiburg, Department of Rheumatology and Center for Chronic Immunodeficiency, Breisacherstr. 115, 79106 Freiburg, Germany., Teixidó Rubio A; Faculty of Medicine and Medical Center, University of Freiburg, Department of Rheumatology and Center for Chronic Immunodeficiency, Breisacherstr. 115, 79106 Freiburg, Germany., Briem JS; Faculty of Medicine and Medical Center, University of Freiburg, Department of Rheumatology and Center for Chronic Immunodeficiency, Breisacherstr. 115, 79106 Freiburg, Germany., Sica MP; Medical Physics Department, Centro Atómico Bariloche, Comisión Nacional de Energía Atómica (CNEA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Avenida E- Bustillo 9500, R8402AGP Río Negro, San Carlos de Bariloche, Argentina; Instituto de Energía y Desarrollo Sustentable, Centro Atómico Bariloche, Comisión Nacional de Energía Atómica (CNEA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Avenida E- Bustillo 9500, R8402AGP Río Negro, San Carlos de Bariloche, Argentina., Sevdali E; Faculty of Medicine and Medical Center, University of Freiburg, Department of Rheumatology and Center for Chronic Immunodeficiency, Breisacherstr. 115, 79106 Freiburg, Germany., Vigolo M; Department of Biochemistry, University of Lausanne, Ch. des Boveresses 155, 1066 Epalinges, Switzerland., Willen L; Department of Biochemistry, University of Lausanne, Ch. des Boveresses 155, 1066 Epalinges, Switzerland., Odermatt P; Faculty of Medicine and Medical Center, University of Freiburg, Department of Rheumatology and Center for Chronic Immunodeficiency, Breisacherstr. 115, 79106 Freiburg, Germany., Istanbullu D; Faculty of Medicine and Medical Center, University of Freiburg, Department of Rheumatology and Center for Chronic Immunodeficiency, Breisacherstr. 115, 79106 Freiburg, Germany., Herr S; Faculty of Medicine and Medical Center, University of Freiburg, Department of Rheumatology and Center for Chronic Immunodeficiency, Breisacherstr. 115, 79106 Freiburg, Germany., Cavallari M; BIOSS Centre for Biological Signalling Studies, University of Freiburg, Schänzlestr. 18, 79104 Freiburg, Germany., Hess H; Merck KGaA, D-64293 Darmstadt, Germany., Rizzi M; Faculty of Medicine and Medical Center, University of Freiburg, Department of Rheumatology and Center for Chronic Immunodeficiency, Breisacherstr. 115, 79106 Freiburg, Germany., Eibel H; Faculty of Medicine and Medical Center, University of Freiburg, Department of Rheumatology and Center for Chronic Immunodeficiency, Breisacherstr. 115, 79106 Freiburg, Germany., Schneider P; Department of Biochemistry, University of Lausanne, Ch. des Boveresses 155, 1066 Epalinges, Switzerland. Electronic address: pascal.schneider@unil.ch.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2022 Mar 29; Vol. 38 (13), pp. 110583.
DOI:	10.1016/j.celrep.2022.110583
Abstrakt:	In mature B cells, TACI controls class-switch recombination and differentiation into plasma cells during T cell-independent antibody responses. TACI binds the ligands BAFF and APRIL. Approximately 10% of patients with common variable immunodeficiency (CVID) carry TACI mutations, of which A181E and C172Y are in the transmembrane domain. Residues A181 and C172 are located on distinct sides of the transmembrane helix, which is predicted by molecular modeling to spontaneously assemble into trimers and dimers. In human B cells, these mutations impair ligand-dependent (C172Y) and -independent (A181E) TACI multimerization and signaling, as well as TACI-enhanced proliferation and/or IgA production. Genetic inactivation of TACI in primary human B cells impaired survival of CpG-activated cells in the absence of ligand. These results identify the transmembrane region of TACI as an active interface for TACI multimerization in signal transduction, in particular for ligand-independent signals. These functions are perturbed by CVID-associated mutations. Competing Interests: Declaration of interests H.H. is employee of Merck KGaA. Other authors declare no competing interests. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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