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Mcl-1 is essential for the survival of plasma cells


Peperzak, V; Vikstrom, I; Walker, J; Glaser, SP; LePage, M; Coquery, CM; Erickson, LD; Fairfax, K; Mackay, F; Strasser, A; Nutt, SL; Tarlinton, DM
2013-03
NATURE IMMUNOLOGY
Journal Article
14
3
290-297
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.
NATURE PUBLISHING GROUP
MEMORY B-CELLS; BONE-MARROW; MULTIPLE-MYELOMA; SMALLPOX VACCINATION; RHEUMATOID-ARTHRITIS; INADEQUATE RESPONSE; CUTTING EDGE; PHASE-II; EXPRESSION; APRIL
Cancer and Haematology; Molecular Genetics of Cancer; Immunology; Molecular Immunology
10.1038/ni.2527
© 2013 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.

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Creation Date 2013-03-01 12:00:00