Ezh2 Knockout in B Cells Impairs Plasmablast Differentiation and Ameliorates Lupus-like Disease in MRL/lpr Mice.

ABSTRACT:

Objectives

EZH2 regulates B cell development and differentiation. We previously demonstrated increased EZH2 expression in peripheral blood mononuclear cells from lupus patients. The goal of this study was to evaluate the role of EZH2 expression in B cells in the pathogenesis of lupus.

Methods

We generated an MRL/lpr mouse with floxed Ezh2, which was crossed with CD19-Cre mice to examine the effect of B cell EZH2 deficiency in MRL/lpr lupus-prone mice. Differentiation of B cells was assessed using flow cytometry. Single-cell RNA sequencing and single-cell B cell receptor sequencing were performed. In vitro B cell culture with an X-box binding protein 1 (XBP1) inhibitor was performed. EZH2 and XBP1 messenger RNA levels in CD19+ B cells isolated from lupus patients and healthy

SUBMITTER: Zheng X 

PROVIDER: S-EPMC10492897 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature