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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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.
The authors declare no competing financial interests.
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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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