title: Identification of a negative regulatory role for spi-C in the murine B cell lineage.
abstract: Spi-C is an E26 transformation-specific family transcription factor that is highly related to PU.1 and Spi-B. Spi-C is expressed in developing B cells, but its function in B cell development and function is not well characterized. To determine whether Spi-C functions as a negative regulator of Spi-B (encoded by Spib), mice were generated that were germline knockout for Spib and heterozygous for Spic (Spib(-/-)Spic(+/-)). Interestingly, loss of one Spic allele substantially rescued B cell frequencies and absolute numbers in Spib(-/-) mouse spleens. Spib(-/-)Spic(+/-) B cells had restored proliferation compared with Spib(-/-) B cells in response to anti-IgM or LPS stimulation. Investigation of a potential mechanism for the Spib(-/-)Spic(+/-) phenotype revealed that steady-state levels of Nfkb1, encoding p50, were elevated in Spib(-/-)Spic(+/-) B cells compared with Spib(-/-) B cells. Spi-B was shown to directly activate the Nfkb1 gene, whereas Spi-C was shown to repress this gene. These results indicate a novel role for Spi-C as a negative regulator of B cell development and function.
authors.affiliation: Department of Microbiology and Immunology, Centre for Human Immunology, Schulich School of Medicine and Dentistry, Collaborative Graduate Program in Developmental Biology, Western University, London, Ontario N6A 5C1, Canada; Division of Genetics and Development, Children's Health Research Institute, Lawson Research Institute, London, Ontario N6C 2V5, Canada; and.
authors.forename: Stephen K H
authors.initials: SK
authors.lastname: Li
authors.affiliation: Department of Microbiology and Immunology, Centre for Human Immunology, Schulich School of Medicine and Dentistry, Collaborative Graduate Program in Developmental Biology, Western University, London, Ontario N6A 5C1, Canada; Division of Genetics and Development, Children's Health Research Institute, Lawson Research Institute, London, Ontario N6C 2V5, Canada; and.
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Solomon
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229.
authors.forename: Patricia C
authors.initials: PC
authors.lastname: Fulkerson
authors.affiliation: Department of Microbiology and Immunology, Centre for Human Immunology, Schulich School of Medicine and Dentistry, Collaborative Graduate Program in Developmental Biology, Western University, London, Ontario N6A 5C1, Canada; Division of Genetics and Development, Children's Health Research Institute, Lawson Research Institute, London, Ontario N6C 2V5, Canada; and rdekoter@uwo.ca.
authors.forename: Rodney P
authors.initials: RP
authors.lastname: DeKoter
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D052002:NF-kappa B p50 Subunit / Q000235:genetics / Q000276:immunology; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000276:immunology
chemical_list: D004268:DNA-Binding Proteins; D052002:NF-kappa B p50 Subunit; D050783:Proto-Oncogene Proteins c-ets; C514177:Spi-B protein, mouse; C423918:Spic protein, mouse; C073701:Nfkb1 protein, mouse