Blimp-1 is required for maintenance of long-lived plasma cells in the bone marrow.
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.
Shapiro-Shelef
Miriam
M
Department of Microbiology, Columbia University College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Lin
Kuo-I
KI
Savitsky
David
D
Liao
Jerry
J
Calame
Kathryn
K
D000818:Animals; D015551:Autoimmunity / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology*; D015870:Gene Expression / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D009101:Multiple Myeloma / Q000188:drug therapy / Q000276:immunology; D010950:Plasma Cells / Q000276:immunology*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011509:Proteoglycans / Q000276:immunology; D012097:Repressor Proteins / Q000276:immunology*; D053668:Syndecan-1; D053667:Syndecans; D014157:Transcription Factors / Q000276:immunology*
D008562:Membrane Glycoproteins; C513258:Prdm1 protein, mouse; D011509:Proteoglycans; D012097:Repressor Proteins; C508241:SDC1 protein, human; C508242:Sdc1 protein, mouse; D053668:Syndecan-1; D053667:Syndecans; D014157:Transcription Factors; D000074462:Positive Regulatory Domain I-Binding Factor 1; D017493:Leukocyte Common Antigens