An interfering form of Blimp-1 increases IgM secreting plasma cells and blocks maturation of peripheral B cells.
B lymphocyte-induced maturation protein-1 (Blimp-1) can drive plasmacytic differentiation in cultured cell models. To determine the role of Blimp-1 in B cell development in vivo, we have generated transgenic mice expressing an interfering truncated form of Blimp-1 (TBlimp) under the control of an immunoglobulin heavy chain promoter and intronic (E) enhancer. TBlimp-transgenic mice have elevated serum IgM and a prolonged IgM response. This effect is due to an increased number of short-lived, IgM-secreting plasma cells resulting from increased proliferation and prolonged survival. In addition, TBlimp-transgenic mice have a developmental defect in the generation of mature B cells in the spleen. These results show that in vivo Blimp-1 plays a fundamental role in the control of the life span and exit from the cell cycle of IgM secreting plasma cells.
Angelin-Duclos
Cristina
C
Departments of Microbiology and Biochemistry and Molecular Biophysics, Columbia University College of Physicians and Surgeons, New York, USA.
Johnson
Kristen
K
Liao
Jerry
J
Lin
Kuo-I
KI
Calame
Kathryn
K
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002453:Cell Cycle; D002454:Cell Differentiation; D002455:Cell Division; D002470:Cell Survival; D007075:Immunoglobulin M / Q000096:biosynthesis*; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011509:Proteoglycans / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D053667:Syndecans; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology*
D007075:Immunoglobulin M; D008562:Membrane Glycoproteins; C513258:Prdm1 protein, mouse; D011509:Proteoglycans; D012097:Repressor Proteins; D053667:Syndecans; D014157:Transcription Factors; D000074462:Positive Regulatory Domain I-Binding Factor 1