Age-associated defects in B lymphocyte development.
The steady-state level of both RAG-1 and RAG-2 mRNA, the number of Pre-B cells, and the number of Pre-B cells expressing RAG-2 protein decrease in the bone marrow of old mice. These differences appear to be due, at least in part, to increased apoptosis of bone marrow Pre-B cells. To determine whether the age-associated increase in apoptosis reflects the impaired expression of the Pre-B cell receptor required for the survival of Pre-B cells, we examined the recombination of D to J and V to DJ in bone marrow from young and old mice. Both D to J recombination, which occurs early in the Pro-B cell stage of development, and V to DJ, which occurs just prior to the transition to the Pre-B cell stage, are diminished with age. These findings support the view that immunoglobulin recombination may impair the expression of the Pre-B cell receptor and may contribute to the increased rate of apoptosis of Pre-B cells in the bone marrow of old mice.
Szabo
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Division of Geriatrics and Gerontology, Weill Medical College of Cornell University, New York, NY 10021, USA.
Shen
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Weksler
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ME
D000375:Aging / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000235:genetics; D015322:Gene Rearrangement, B-Lymphocyte; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D018398:Homeodomain Proteins / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D012333:RNA, Messenger; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein