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In Vitro Differentiation Model of Human Normal Memory B Cells to Long-lived Plasma Cells
Published on: January 20, 2019
Increased let-7b-5p is associated with enhanced BAFF-R expression and B cell survival in immune thrombocytopenia
Yao Wang1, Xi Jia1, Ling Zhou2
1MOE Engineering Center of Hematological Disease, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, Soochow University, Suzhou 215006, Jiangsu Province, China.
Background:
B cells play a key role in the pathogenesis of immune thrombocytopenia (ITP) by producing platelet autoantibodies. Accumulating evidence suggest that microRNA (miRNA) is a critical regulator in B cells. The contribution of miRNA to B cell dysfunction in ITP has not been described. The aim of this study was to examine the expression of miRNA let-7b-5p in B cells of ITP patients and investigate its possible association with B cell function in ITP.
Methods:
The CD19+ cells were isolated from peripheral mononuclear cells of ITP patients and healthy controls using immunomagnetic microbeads. B cell survival in vitro was evaluated by cell counting. The level of let-7b-5p was quantified by quantitative PCR. The surface expression of B cell activating factor receptor (BAFF-R) was detected by flow cytometry. The role of let-7b-5p was examined in isolated B cells by transfecting miRNA mimics or inhibitors.
Results:
The results showed that let-7b-5p in B cells was elevated, and B cell survival was enhanced in ITP patients compared with healthy controls. BAFF and B cell receptor stimulation can induce the expression of let-7b-5p in vitro. Overexpression of let-7b-5p in B cells enhanced the expression of surface BAFF-R and promoted B cell survival. Moreover, let-7b-5p enhanced the phosphorylation of NF-κB2 p100 and upregulated the expression of survival factor Bcl-xL after BAFF induction.
Conclusion:
Let-7b-5p is a pro-survival miRNA in B cells and increased let-7b-5p is associated with enhanced surface BAFF-R in ITP.

