title: Distinct Genetic Networks Orchestrate the Emergence of Specific Waves of Fetal and Adult B-1 and B-2 Development.
abstract: B cell development is often depicted as a linear process initiating in the fetus and continuing postnatally. Using a PU.1 hypomorphic mouse model, we found that B-1 and B-2 lymphopoiesis occurred in distinct fetal and adult waves differentially dependent on the Sfpi1 14 kB upstream regulatory element. The initial wave of fetal B-1 development was absent in PU.1 hypomorphic mice, while subsequent fetal and adult waves emerged. In contrast, B-2 lymphopoiesis occurred in distinct fetal and adult waves. Whole-transcriptome profiling of fetal and adult B cell progenitors supported the existence of three waves of B-1 and two waves of B-2 development and revealed that the network of transcription factors governing B lineage specification and commitment was highly divergent between B-1 and B-2 progenitors. These findings support the view that the B-1 and B-2 lineages are distinct and provide a genetic basis for layering of immune system development.
authors: Department of Pathology and Laboratory Medicine, Division of Hematology/Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors: Encarnacion
authors: E
authors: Montecino-Rodriguez
authors: Department of Pathology and Laboratory Medicine, Division of Hematology/Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors: Michael
authors: M
authors: Fice
authors: Department of Pathology and Laboratory Medicine, Division of Hematology/Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors: David
authors: D
authors: Casero
authors: Department of Medicine, Division of Hematology/Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors: Beata
authors: B
authors: Berent-Maoz
authors: Department of Biology, California Lutheran University, Thousand Oaks, CA 91360, USA.
authors: Chad L
authors: CL
authors: Barber
authors: Department of Pathology and Laboratory Medicine, Division of Hematology/Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: kdorshki@mednet.ucla.edu.
authors: Kenneth
authors: K
authors: Dorshkind
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D019070:Cell Lineage / Q000276:immunology; D005333:Fetus / Q000276:immunology; D020869:Gene Expression Profiling / Q000379:methods; D053263:Gene Regulatory Networks / Q000276:immunology*; D038041:Lymphopoiesis / Q000276:immunology*; D051379:Mice; D054448:Precursor Cells, B-Lymphoid / Q000276:immunology; D014157:Transcription Factors / Q000276:immunology
chemical_list: D014157:Transcription Factors