Both multiorgan inflammation and myeloid hyperplasia in RelB-deficient mice are T cell dependent.
Mice with a targeted disruption of RelB, a member of the Rel/NF-kappaB family of transcription factors, have multifocal, mixed inflammatory cell infiltration in several organs, myeloid hyperplasia, and splenomegaly due to extramedullary hemopoiesis. To elucidate the cellular requirements for this complex phenotype, we have bred RelB-deficient (RelB(kappaO)) animals to two strains of immunodeficient mice, recombinase-activating gene-1-deficient (RAG-1(kappaO), lacking B and T cells), and Nur77/N10-transgenic mice (Nur77/N10(TG), lacking only T cells). We also generated mutant mice deficient in both RelB and the p50 subunit of NF-kappaB (p50(kappaO), multiple defects in B cell function). RelB(kappaO)RAG-1(kappaO) and RelB(kappaO)Nur77/N10(TG) mice are disease-free, while RelB(kappaO)p50(kappaO) double-mutant animals develop an even more severe phenotype despite the absence of B cells in the inflammatory infiltrates. Thus, both multiorgan inflammation and myeloid hyperplasia in RelB-deficient mice are T cell dependent, whereas B cells are not crucially involved.
Department of Oncology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543, USA.
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Weih
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Durham
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Barton
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Sha
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Baltimore
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Bravo
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001853:Bone Marrow / Q000276:immunology / Q000473:pathology*; D003433:Crosses, Genetic; D018398:Homeodomain Proteins; D006965:Hyperplasia; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D007249:Inflammation / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D011506:Proteins / Q000502:physiology; D011518:Proto-Oncogene Proteins; D013163:Splenomegaly / Q000209:etiology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*; D051841:Transcription Factor RelB; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics / Q000502:physiology
D018398:Homeodomain Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; C497594:Relb protein, mouse; D014157:Transcription Factors; C064658:RAG-1 protein; D051841:Transcription Factor RelB