BMP-6 inhibits growth of mature human B cells; induction of Smad phosphorylation and upregulation if Id1

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Abstract

Background: Bone morphogenetic proteins (BMPs) belong to the TGF-β superfamily and are secreted proteins with pleiotropic roles in many different cell types. A potential role of BMP-6 in the immune system has been implied by various studies of malignant and rheumatoid diseases. In the present study, we explored the role of BMP-6 in normal human peripheral blood B cells. Results: The B cells were found to express BMP type I and type II receptors and BMP-6 rapidly induced phosphorylation of Smad1/5/8. Furthermore, Smad-phosphorylation was followed by upregulation of Id1 mRNA and Id1 protein, whereas Id2 and Id3 expression was not affected. Furthermore, we found that BMP-6 had an antiproliferative effect both in naïve (CD19+CD27-) and memory B cells (CD19+CD27+) stimulated with anti-IgM alone or the combined action of anti-IgM and CD40L. Additionally, BMP-6 induced cell death in activated memory B cells. Importantly, the antiproliferative effect of BMP-6 in B-cells was completely neutralized by the natural antagonist, noggin. Furthermore, B cells were demonstrated to upregulate BMP-6 mRNA upon stimulation with anti-IgM. Conclusion: In mature human B cells, BMP-6 inhibited cell growth, and rapidly induce phosphorylation of Smad1/5/8 followed by an upregulation of Id1. © 2005 Kersten et al; licensee BioMed Central Ltd.

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Kersten, C., Sivertsen, E. A., Hystad, M. E., Forfang, L., Smeland, E. B., & Myklebust, J. H. (2005). BMP-6 inhibits growth of mature human B cells; induction of Smad phosphorylation and upregulation if Id1. BMC Immunology, 6. https://doi.org/10.1186/1471-2172-6-9

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