Activation of the recombination activating gene 1 (RAG-1) transcript in bone marrow of senescent C57BL/6 mice by recombinant interleukin-7

J Gerontol A Biol Sci Med Sci. 1999 Apr;54(4):B143-8. doi: 10.1093/gerona/54.4.b143.

Abstract

The level of the recombination activating gene 1 (RAG-1) mRNA in bone marrow cells decreases to a minimal level by the age of 10 months. Recominbant interleukin-7 (rIL-7) is a potent proliferative stimulus for B cell progenitors and upregulates RAG-1 expression in lymphocyte precursors. To investigate the stimulatory effect of rIL-7 on the expression of RAG-1 in old mice, we compared the level of RAG-1 message in short-term bone marrow cultures of cells from mice aged 1 month and 18 months. We found similar levels of RAG-1 mRNA in bone marrow cells of young mice before and after 24 hours of incubation. No RAG-1 mRNA was detected in bone marrow cell cultures prepared from old mice after 24 hours of incubation. However, when rIL-7 was added to the culture medium, RAG-1 mRNA was detected after 24 hours of incubation and its level was similar to that measured in cells from young mice. The expression of RAG-1 was dose-dependent, with 20 ng of rIL-7 per 10(6) old nucleated cells yielding the maximal response. Our results indicate that despite the low or no RAG-1 expression in bone marrow cultures of old mice, the potential to activate RAG-1 in B-cell precursors is still present, and immunoglobulin heavy chain (V(H)D(H)J(H)) rearrangement may be enhanced by rIL7.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / genetics*
  • Aging / metabolism
  • Animals
  • B-Lymphocytes / metabolism
  • Bone Marrow Cells / metabolism*
  • Cell Division
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Female
  • Gene Expression Regulation*
  • Gene Rearrangement, B-Lymphocyte, Heavy Chain
  • Genes, RAG-1 / genetics*
  • Hematopoietic Stem Cells / metabolism
  • Interleukin-7 / administration & dosage
  • Interleukin-7 / pharmacology*
  • Lymphocytes / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • RNA, Messenger / genetics
  • Recombinant Proteins
  • Transcription, Genetic / genetics*
  • Up-Regulation

Substances

  • Interleukin-7
  • RNA, Messenger
  • Recombinant Proteins