The age-related decrease in E47 DNA-binding does not depend on increased Id inhibitory proteins in bone marrow-derived B cell precursors.
Our previous results showed that decreased numbers of pre-B cells in aged mice were associated with decreases in surrogate light chain, lambda5, and transcription factors E47/E12. In the present paper, we have analyzed IL-7-expanded populations of pro-B/early pre-B cells to evaluate whether the age-related reduction in E47 DNA-binding could be attributed to reduced E47 expression and/or increased Id expression. According to the percentage of pre-B cells present in their bone marrow, old mice were classified as severely depleted (>80% loss in pre-B cells, 50% loss in pro-B cells), or moderately depleted (20-80% loss in pre-B cells). Results herein show that IL-7-stimulated pro-B/pre-B cells from both severely depleted and moderately depleted old mice exhibit a reduced E47 DNA-binding capacity compared to young mice, and this defect in severely depleted old mice is more dramatic than that in moderately depleted old mice. Id proteins, which are inhibitors of E47, are not increased in nuclear extracts of IL-7-expanded pro-B/early pre-B cells from severely depleted or moderately depleted old mice. We therefore conclude that the reduced expression of E47 protein alone in severely depleted and to a lesser extent in moderately depleted old mice explains the reduced amount of E47-DNA binding.
Frasca
Daniela
D
Department of Microbiology and Immunology, University of Miami School of Medicine, 1600 N.W. 10th Ave, Miami, FL 33136, USA. dfrasca@med.miami.edu
Nguyen
Diep
D
Van der Put
Elaine
E
Riley
Richard L
RL
Blomberg
Bonnie B
BB
D000367:Age Factors; D000818:Animals; D001402:B-Lymphocytes / Q000737:chemistry* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000737:chemistry; D002454:Cell Differentiation / Q000502:physiology; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006131:Growth Inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D018257:Helix-Loop-Helix Motifs / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000737:chemistry* / Q000378:metabolism; D051798:Inhibitor of Differentiation Protein 1; D051797:Inhibitor of Differentiation Protein 2; D015851:Interleukin-7 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012097:Repressor Proteins; D013194:Staining and Labeling; D051820:TCF Transcription Factors; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors / Q000096:biosynthesis / Q000378:metabolism*
D004268:DNA-Binding Proteins; D006131:Growth Inhibitors; C497455:Idb1 protein, mouse; C497452:Idb2 protein, mouse; D051798:Inhibitor of Differentiation Protein 1; D051797:Inhibitor of Differentiation Protein 2; D015851:Interleukin-7; D012097:Repressor Proteins; D051820:TCF Transcription Factors; C544913:Tcf7l1 protein, mouse; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors; D004247:DNA