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

Alessandro Camponeschi, Laura Todi, Cristina Cristofoletti, Cristina Lazzeri, Maurizio Carbonari, Milica Mitrevski, Ramona Marrapodi, Martina Del Padre, Massimo Fiorilli, Milvia Casato, Marcella Visentini

Research output: Contribution to journalArticlepeer-review

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 pronounced proliferative defect.

Original languageEnglish
Pages (from-to)7-11
Number of pages5
JournalImmunology Letters
Volume198
DOIs
Publication statusPublished - Jun 2018

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