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Mcl-1 is essential for the survival of plasma cells

Nature Immunology volume 14, pages 290–297 (2013)Cite this article

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A Corrigendum to this article was published on 19 July 2013

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Abstract

The long-term survival of plasma cells is entirely dependent on signals derived from their environment. These extrinsic factors presumably induce and sustain the expression of antiapoptotic proteins of the Bcl-2 family. It is uncertain whether there is specificity among Bcl-2 family members in the survival of plasma cells and whether their expression is linked to specific extrinsic factors. We found here that deletion of the gene encoding the antiapoptotic protein Mcl-1 in plasma cells resulted in rapid depletion of this population in vivo. Furthermore, we found that the receptor BCMA was needed to establish high expression of Mcl-1 in bone marrow but not spleen plasma cells and that establishing this survival pathway preceded the component of plasma cell differentiation that depends on the transcriptional repressor Blimp-1. Our results identify a critical role for Mcl-1 in the maintenance of plasma cells.

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Figure 1: Expression of prosurvival members of the Bcl-2 family in plasma cells.
Figure 2: BCMA regulates Mcl-1 expression in bone marrow plasma cells.
Figure 3: The BCMA pathway is regulated independent of Blimp-1.
Figure 4: Dependence on Mcl-1 in in vitro cultured plasmablasts.
Figure 5: Mcl-1 expression is required for the survival of plasma cells.
Figure 6: Dependence of plasma cells on Mcl-1 is cell intrinsic.

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  • 21 March 2013

    In the version of this article initially published, the number for the National Health and Medical Research Council grant to I.V. is incorrect in the Acknowledgements section. The correct number is 1021374. The error has been corrected in the HTML and PDF versions of the article.

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Acknowledgements

We thank the facilities of our respective institutes, particularly those responsible for animal husbandry and flow cytometry; and C. Wellard, S. Chevrier, D. Segal, D. Huang, S. Heinzel, J. Marchingo, S. Willis and P. Bouillet for assistance. Supported by the Australia National Health and Medical Research Council (1021374 to I.V.; 356202 to D.M.T. and S.L.N.; 461221 to A.S.; 637326 to S.P.G.; 516786 to K.F.; and the Independent Research Institute Infrastructure Support Scheme), the Multiple Myeloma Research Foundation USA (V.P.), the European Molecular Biology Organization (V.P.), the US National Institutes of Health (AI093722 to L.D.E.) and Victorian State Government Operational Infrastructure Support.

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Author notes

  1. Jennifer Walker

    Present address: Present address: Medical Research Council, Laboratory of Molecular Biology, Cambridge, UK.,

  2. Victor Peperzak and Ingela Vikström: These authors contributed equally to this work.

Authors and Affiliations

  1. The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia

    Victor Peperzak, Ingela Vikström, Jennifer Walker, Stefan P Glaser, Andreas Strasser, Stephen L Nutt & David M Tarlinton

  2. Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia

    Victor Peperzak, Ingela Vikström, Stefan P Glaser, Andreas Strasser, Stephen L Nutt & David M Tarlinton

  3. Department of Immunology, Monash University, Melbourne, Victoria, Australia

    Melanie LePage, Kirsten Fairfax & Fabienne Mackay

  4. Department of Microbiology, University of Virginia, Charlottesville, Virginia, USA

    Christine M Coquery & Loren D Erickson

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Contributions

V.P., I.V. and D.M.T. designed the research; V.P., I.V., J.W., S.P.G., M.L., C.M.C. and K.F. did experiments and contributed to interpretation and discussion; L.D.E., F.M., A.S. and S.L.N. contributed to the design of experiments, interpretation of results, and drafting the manuscript; V.P. and I.V. analyzed data and prepared figures; and V.P., I.V. and D.M.T. wrote the manuscript.

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Correspondence to David M Tarlinton.

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Peperzak, V., Vikström, I., Walker, J. et al. Mcl-1 is essential for the survival of plasma cells. Nat Immunol 14, 290–297 (2013). https://doi.org/10.1038/ni.2527

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