Background: The pathogenesis of immune thrombocytopenia (ITP) has not yet been completely elucidated. It has been shown that B cell activating factor BAFF is overexpressed ITP patients and dysregulated miRNAs contribute to ITP pathogenesis. However, it is unclear that whether BAFF can affect B cell function through regulating miRNA levels in ITP.

Aims: We aimed to investigate whether and how BAFF affect B cell homeostasis through regulating miRNA levels in ITP.

Methods: The CD19⁺ B cells were isolated from peripheral mononuclear cells of ITP patients and healthy controls using immunomagnetic microbeads. The miRNA levels were detected by real-time quantitative PCR. The function of miRNAs in B cell were verified in primary human B cells and in a splenocytes transferring model by transfecting miRNA mimics or inhibitors. B cell survival and antibody production were evaluated by flow cytometry and enzyme-linked immunosorbent assay, respectively.

Results: Our results showed that plasma BAFF was significantly elevated in ITP patients with positive platelet autoantibodies and the expression of let-7b was significantly increased in B cells from ITP patients. We found that plasma BAFF was positively correlated with the let-7b level in B cells in ITP patients. Transfection of let-7b mimics into healthy primary B cells enhanced BAFF-induced B cell survival and antibody production in vitro, while transfection of let-7b inhibitors showed opposite effects. We also found that transfection of let-7b inhibitors into immunized mouse CD61 knockout splenocytes which were then transferred to SCID mice, can abolish platelet antibody production in vivo.

Conclusions: Elevated plasma BAFF can promote B cell survival and autoantibody production through upregulating let-7b levels in ITP.

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/elevated-baff-promote-b-cell-survival-and-autoantibody-production-through-upregulating-let-7b-in-immune-thrombocytopenia/