1. DEC1/STRA13 is a key negative regulator of activation-induced proliferation of human B cells highly expressed in anergic cells.
- Author
-
Camponeschi A, Todi L, Cristofoletti C, Lazzeri C, Carbonari M, Mitrevski M, Marrapodi R, Del Padre M, Fiorilli M, Casato M, and Visentini M
- Subjects
- Basic Helix-Loop-Helix Transcription Factors genetics, Cell Cycle, Cell Proliferation, Cells, Cultured, Cryoglobulinemia genetics, Cryoglobulinemia immunology, Cryoglobulinemia pathology, Gene Expression Regulation immunology, Gene Knockdown Techniques, Hepatitis C genetics, Hepatitis C immunology, Hepatitis C pathology, Homeodomain Proteins genetics, Humans, RNA, Small Interfering metabolism, Receptors, Antigen, B-Cell metabolism, Signal Transduction, Toll-Like Receptor 9 metabolism, B-Lymphocytes immunology, Basic Helix-Loop-Helix Transcription Factors metabolism, Clonal Anergy, Homeodomain Proteins metabolism, Lymphocyte Activation
- Abstract
The transcription factor DEC1/STRA13 (also known as BHLHE40 and SHARP2) is involved in a number of processes including inhibition of cell proliferation and delay of cell cycle, and is a negative regulator of B cell activation and development in mice. We show here that, unlike in mice, DEC1/STRA13 expression is induced in human naïve and memory resting B cells by activation through the B-cell receptor (BCR) or Toll-like receptor 9 (TLR9). siRNA silencing of DEC1/STRA13 increases the capacity of activated B cells to perform a high number of divisions after TLR9 ligation. This identifies DEC1/STRA13 as a critical negative regulator of clonal expansion of activated human B cells. We also show that DEC1/STRA13 is upregulated in human anergic CD21
low B cells clonally expanded in patients with HCV-associated mixed cryoglobulinemia, which fail to proliferate in response to BCR or TLR9 ligation. siRNA knockdown of DEC1/STRA13, however, fails to restore responsiveness to stimuli in these cells, although it might improve the proliferative capacity in a subset of anergic cells with less pronounced proliferative defect., (Copyright © 2018 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.)- Published
- 2018
- Full Text
- View/download PDF