Loss in CD19 B Cells Promotes Megakaryocytopoiesis Via IL-6/STAT3 Signaling-mediated Thrombopoietin Production

: Aurora kinase A (Aurora-A), which is required for mitosis, is a therapeutic target in various tumors. Targeting Aurora-A led to an increase in the differentiation and polyploidization of megakaryocytes both and . However, the mechanisms involved in controlling megakaryocyte differentiation have not been fully elucidated. Conditional knockout mice were generated. B cell development, platelet development and function were subsequently examined. Proplatelet formation, response to mTPO, post-transfusion experiment, colony assay, immunofluorescence staining and quantification, and ChIP assay were conducted to gain insights into the mechanisms of loss in megakaryocytopoiesis. Loss of in CD19 B cells impaired B cell development in association with an increase in the number of platelets in peripheral blood (PB). Surprisingly, thrombopoietin (TPO) production and IL-6 were elevated in the plasma in parallel with an increase in the number of differentiated megakaryocytes in the bone marrow (BM) of mice. Interestingly, compared with that of the mice, a higher number of CD19 B cells close to megakaryocytes was observed in the BM of the mice. Moreover, loss in CD19 B cells induced signal transducer and activator of transcription-3 (STAT3) activation. Inhibition of STAT3 reduced the mRNA levels. ChIP assays revealed that STAT3 bound to the TPO promoter. Additionally, STAT3-mediated TPO transcription was an autocrine effect provoked by IL-6, at least partially. Deletion of in CD19 B cells led to an increase in IL-6 production, promoting STAT3 activation, which in turn contributed to TPO transcription and megakaryocytopoiesis.