Commitment of B lymphocytes to a plasma cell fate is associated with Blimp-1 expression in vivo.
B lymphocyte-induced maturation protein-1 (Blimp-1) is a transcriptional repressor that is sufficient to trigger terminal differentiation in the B cell lymphoma BCL-1. In this study, we have determined the expression pattern of Blimp-1 in vivo in primary and secondary lymphoid organs of humans and immunized mice. Blimp-1 is expressed in plasma cells derived from either a T-independent or T-dependent response in plasma cells that have undergone isotype switching and those resulting from secondary immunization. Blimp-1 is also present in long-lived plasma cells residing in the bone marrow. However, Blimp-1 was not detected in memory B cells. This expression pattern provides further evidence of a critical role for Blimp-1 in plasma cell development, supporting earlier studies in cultured lines. Significantly, Blimp-1 was also found in a fraction (4-15%) of germinal center B cells in murine spleen and human tonsils. Blimp-1 expression in the germinal center is associated with an interesting subset of cells with a phenotype intermediate between germinal center B cells and plasma cells. In the mouse, Blimp-1(+) germinal center B cells peak at day 12 postimmunization and disappear soon thereafter. They are not apoptotic, some are proliferating, they express germinal center markers peanut agglutinin or CD10 but not Bcl-6, and most express CD138 (syndecan-1), IRF4, and cytoplasmic Ig. Together, these data support a model in which B cell fate decisions occur within the germinal center and Blimp-1 expression is critical for commitment to a plasma cell, rather than a memory cell, fate.
Angelin-Duclos
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Departments of Microbiology and Pathology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Cattoretti
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Lin
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KI
Calame
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K
D000818:Animals; D000955:Antigens, T-Independent / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology; D005362:Ficoll / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000276:immunology; D018858:Germinal Center / Q000166:cytology; D006241:Haptens / Q000008:administration & dosage / Q000276:immunology; D006433:Hemocyanins / Q000008:administration & dosage / Q000276:immunology; D006801:Humans; D007117:Immunization, Secondary; D007156:Immunologic Memory; D016130:Immunophenotyping; D007274:Injections, Intraperitoneal; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D009596:Nitrophenols / Q000008:administration & dosage / Q000276:immunology; D010648:Phenylacetates; D010950:Plasma Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D012097:Repressor Proteins; D014157:Transcription Factors / Q000096:biosynthesis*
C042158:2,4-dinitrophenyl keyhole limpet hemocyanin; D000955:Antigens, T-Independent; C031007:DNP-Ficoll; D006241:Haptens; D009596:Nitrophenols; D010648:Phenylacetates; C513258:Prdm1 protein, mouse; D012097:Repressor Proteins; D014157:Transcription Factors; C026242:4-hydroxy-5-nitrophenyl acetic acid; C087042:PRDM1 protein, human; D005362:Ficoll; D006433:Hemocyanins; D000074462:Positive Regulatory Domain I-Binding Factor 1