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

• Published in: The Journal of experimental medicine Vol. 202; no. 11; pp. 1471 - 1476
• Main Authors: Shapiro-Shelef, Miriam, Lin, Kuo-I, Savitsky, David, Liao, Jerry, Calame, Kathryn
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 05.12.2005
• Subjects: Animals; Autoimmunity - immunology; Bone Marrow Cells - immunology; Brief Definitive Report; Gene Expression - immunology; Leukocyte Common Antigens - immunology; Membrane Glycoproteins - immunology; Mice; Mice, Knockout; Multiple Myeloma - drug therapy; Multiple Myeloma - immunology; Plasma Cells - immunology; Positive Regulatory Domain I-Binding Factor 1; Proteoglycans - immunology; Repressor Proteins - immunology; Syndecan-1; Syndecans; Transcription Factors - immunology
• ISSN: 0022-1007; 1540-9538; 1892-1007
• DOI: 10.1084/jem.20051611

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 B220(LO)CD138(HI) 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.