Article ; Online: Ligand-independent oligomerization of TACI is controlled by the transmembrane domain and regulates proliferation of activated B cells.
2022 Volume 38, Issue 13, Page(s) 110583
Abstract: 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 ( ... ...
| Abstract | 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. |
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| MeSH term(s) | B-Lymphocytes ; Cell Proliferation ; Common Variable Immunodeficiency/genetics ; Common Variable Immunodeficiency/metabolism ; Humans ; Ligands ; Transmembrane Activator and CAML Interactor Protein/genetics ; Transmembrane Activator and CAML Interactor Protein/metabolism |
| Chemical Substances | Ligands ; Transmembrane Activator and CAML Interactor Protein |
| Language | English |
| Publishing date | 2022-03-27 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2649101-1 |
| ISSN | 2211-1247 ; 2211-1247 |
| ISSN (online) | 2211-1247 |
| ISSN | 2211-1247 |
| DOI | 10.1016/j.celrep.2022.110583 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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