The Journal of Experimental Medicine
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Published online 28 November 2005 doi:10.1084/jem.20051611
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 202, Number 11, 1471-1476
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BRIEF DEFINITIVE REPORT

 Blimp-1 is required for maintenance of long-lived plasma cells in the bone marrow

Miriam Shapiro-Shelef1, Kuo-I Lin1, David Savitsky2, Jerry Liao1, and Kathryn Calame1

1 Department of Microbiology, Columbia University College of Physicians and Surgeons
2 Department of Biological Sciences, Columbia University, New York, NY 10032

CORRESPONDENCE Kathryn Calame: KLC1{at}columbia.edu

Long-lived plasma cells, residing primarily in the bone marrow, continuously secrete antibody and provide an important component of humoral memory. However, when such cells secrete autoantibodies or become transformed, they can be pathogenic. We have shown recently that the transcriptional repressor B lymphocyte–induced maturation protein 1 (Blimp-1) is required for the formation of plasma cells. To determine what role Blimp-1 might play in maintenance of plasma cells, we generated mice in which the gene encoding Blimp-1 could be deleted in an inducible manner. Deletion of Blimp-1 either in vitro or in vivo leads to loss of previously formed B220LOCD138HI plasma cells. Using BrdU incorporation, we confirmed that Blimp-1 is required for the maintenance of nondividing, long-lived plasma cells in the bone marrow. Blimp-1 is also required for long-term maintenance of antigen-specific immunoglobulin in serum. Thus Blimp-1 is required not only for the formation but also for the maintenance of long-lived plasma cells. This finding provides the possibility of new drug design strategies for autoimmunity and multiple myeloma focused on blocking Blimp-1 expression or activity.

K-I. Lin's present address is The Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.


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