Modular nature of Blimp-1 in the regulation of gene expression during B cell maturation.
The transcription factor Blimp-1 induces the maturation of B cells into Ab-secreting plasma cells. DNA microarrays were used to analyze the transcription profiles of both Blimp-1-transduced murine B cell lines and the inducible B cell line BCL(1). Hundreds of genes were differentially regulated, showing how Blimp-1 both restricts affinity maturation and promotes Ab secretion, homeostasis, migration, and differentiation. Strikingly, when different modes of plasma cell induction are used, very different genetic programs are used, suggesting that the transition from a B cell to plasma cell can occur in multiple ways, perhaps accounting for the different types of Ab-secreting cells observed in vivo. Furthermore, mutagenesis of Blimp-1 reveals multiple effector domains, which regulate distinct genes. This indicates that Blimp-1 subdivides the maturation program into select and tunable pathways.
Sciammas
Roger
R
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA. rsciamma@uchicago.edu
Davis
Mark M
MM
D020413:3' Untranslated Regions / Q000378:metabolism; D020816:Amino Acid Motifs / Q000235:genetics / Q000276:immunology; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D002448:Cell Adhesion / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics* / Q000276:immunology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology*; D007136:Immunoglobulins / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000235:genetics; D008223:Lymphoma / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D016254:Mutagenesis, Insertional; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D018384:Oxidative Stress / Q000235:genetics / Q000276:immunology; D000074462:Positive Regulatory Domain I-Binding Factor 1; D017434:Protein Structure, Tertiary / Q000235:genetics; D012323:RNA Processing, Post-Transcriptional / Q000276:immunology; D012097:Repressor Proteins / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D014157:Transcription Factors / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D014161:Transduction, Genetic
D020413:3' Untranslated Regions; D007136:Immunoglobulins; C513258:Prdm1 protein, mouse; D012097:Repressor Proteins; D014157:Transcription Factors; D000074462:Positive Regulatory Domain I-Binding Factor 1