| Abstract: |
We have previously reported that bone marrow B cell precursors from thymic-deprived nude and old mice express less recombination-activating gene- 1 (RAG-1) mRNA than they do in young euthymic mice. We now report that both nude and old mice have decreased bone marrow pre-B cells and that fewer pre- B cells express RAG protein. This combination of events appears to be the basis for the lower level of bone marrow RAG mRNA in thymic-deprived mice. A link between thymic function and B cell development was suggested by the similar kinetics of thymic involution and of declining bone marrow RAG-1 gene expression during aging. Support for this hypothesis was obtained by demonstrating that injection of supernatant medium from activated CD8+ but not CD4+ young T cells from mice increases RAG mRNA, RAG protein, and the number of bone marrow pre-B cells in nude and old mice. Furthermore, in vivo CD8+ T cells also regulate bone marrow RAG gene expression. Thus, mice deficient in CD8+ T cells expressed levels of RAG-1 mRNA in their bone marrow that were only 10% of those observed in normal or CD4+ T cell- deficient mice. IL-16 was detected in the supernatant medium from activated T cell cultures, and injection of nanogram quantities of recombinant IL-16 (rIL-16) into nude or old mice increased the levels of RAG mRNA in bone marrow B cell precursors and the number of bone marrow pre-B cells. We conclude that the impaired development of B cells within the bone marrow of thymic-deprived nude and old mice can be reversed, at least in part, by the administration of rIL-16. |
| Keywords: |
controlled study; unclassified drug; nonhuman; cd8 antigen; cd8-positive t-lymphocytes; t-lymphocytes; animal cell; mouse; animals; mice; mice, knockout; bone marrow cells; gene expression; cell maturation; animal experiment; animal model; gene product; cell differentiation; homeodomain proteins; mice, inbred balb c; mice, inbred c57bl; b lymphocyte; b-lymphocytes; lymphocyte activation; genetic recombination; nude mouse; mice, nude; thymus gland; messenger rna; rna, messenger; stem cells; aging; bone marrow cell; cd4 antigen; dna nucleotidylexotransferase; t lymphocyte activation; lymphocyte count; injections, intravenous; interleukin 16; cell-free system; genes, rag-1; prolymphocyte; female; priority journal; article; recombinant interleukin 16; interleukin-16
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