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Transformation of mature mouse B cells into malignant plasma cells in vitro via introduction of defined genetic elements
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
Number of Authors: 42019 (English)In: European Journal of Immunology, ISSN 0014-2980, E-ISSN 1521-4141, Vol. 49, no 3, p. 454-461Article in journal (Refereed) Published
Abstract [en]

An experimental system where defined alterations in gene function or gene expression levels in primary B cells would result in the development of transformed plasma cells in vitro would be useful in order to facilitate studies of the underlying molecular mechanisms of plasma cell malignancies. Here, such a system is described in which primary murine B cells rapidly become transformed into surface CD138(+), IgM(-/low), CD19(-) IgM-secreting plasma cells as a result of expression of the transcription factors IRF4 and MYC together with simultaneous expression of BMI1, mutated p53 or silencing of p19(Arf), and suppression of intrinsic apoptosis through expression of BCLXL. Analysis of gene expression patterns revealed that this combination of transforming genes resulted in expression of a number of genes previously associated with terminally differentiated B cells (plasma cells) and myeloma cells, whereas many genes associated with mature B cells and B-cell lymphomas were not expressed. Upon transplantation, the transformed cells preferentially localized to the bone marrow, presenting features of a plasma cell malignancy of the IgM isotype. The present findings may also be applicable in the development of novel methods for production of monoclonal antibodies.

Place, publisher, year, edition, pages
2019. Vol. 49, no 3, p. 454-461
Keywords [en]
Apoptosis, Monoclonal antibodies, MYC, p53, Plasma cell malignancies
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:su:diva-167625DOI: 10.1002/eji.201847855ISI: 000460473800010PubMedID: 30664244OAI: oai:DiVA.org:su-167625DiVA, id: diva2:1304454
Available from: 2019-04-12 Created: 2019-04-12 Last updated: 2019-04-12Bibliographically approved

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Lindvall, Jessica M.
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