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 CD21low 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 pro- nounced proliferative defect.

DEC1/STRA13 is a key negative regulator of activation-induced proliferation of human B cells highly expressed in anergic cells / Camponeschi, Alessandro; Todi, Laura; Cristofoletti, Cristina; Lazzeri, Cristina; Carbonari, Maurizio; Mitrevski, Milica; Marrapodi, Ramona; DEL PADRE, Martina; Fiorilli, Massimo; Casato, Milvia; Visentini, Marcella. - In: IMMUNOLOGY LETTERS. - ISSN 0165-2478. - STAMPA. - 198(2018), pp. 7-11. [10.1016/j.imlet.2018.03.014]

DEC1/STRA13 is a key negative regulator of activation-induced proliferation of human B cells highly expressed in anergic cells

CAMPONESCHI, ALESSANDRO;Laura Todi;Cristina Cristofoletti;Cristina Lazzeri;Maurizio Carbonari;Milica Mitrevski;MARRAPODI, RAMONA;Martina Del Padre;Massimo Fiorilli;Milvia Casato;Marcella Visentini
2018

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 CD21low 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 pro- nounced proliferative defect.
2018
Activation, Anergy, B cells, Cryoglobulinemia, DEC1/STRA13, Proliferation, siRNA
01 Pubblicazione su rivista::01a Articolo in rivista
DEC1/STRA13 is a key negative regulator of activation-induced proliferation of human B cells highly expressed in anergic cells / Camponeschi, Alessandro; Todi, Laura; Cristofoletti, Cristina; Lazzeri, Cristina; Carbonari, Maurizio; Mitrevski, Milica; Marrapodi, Ramona; DEL PADRE, Martina; Fiorilli, Massimo; Casato, Milvia; Visentini, Marcella. - In: IMMUNOLOGY LETTERS. - ISSN 0165-2478. - STAMPA. - 198(2018), pp. 7-11. [10.1016/j.imlet.2018.03.014]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1121402
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