Bone marrow declines as a site of B-cell precursor differentiation with age: Relationship to thymus involution Journal Article
| Authors: | Ben-Yehuda, A.; Szabo, P.; Dyall, R.; Weksler, M. E. |
| Article Title: | Bone marrow declines as a site of B-cell precursor differentiation with age: Relationship to thymus involution |
| Abstract: | The rearrangement of immunoglobulin genes in B-lymphocyte precursors requires the expression of the recombination activating genes (Rag), which leads to the generation of a highly diverse B-cell repertoire. We can use the level of Rag-1 mRNA in the bone marrow as an index of its capacity to support the maturation of B lymphocytes as all detectable bone marrow Rag-1 mRNA is expressed by B-cell precursors. In mouse bone marrow, Rag-1 mRNA increases during the first 2 months of life to reach its maximal level at 2 months of age. This level is maintained until 5 months of age and thereafter declines to a minimum level by 10 months of age. Thus, bone marrow Rag-1 mRNA is highest at the time when thymic function is maximal in euthymic mice. An association between thymic activity and bone marrow Rag-1 gene expression was supported by showing a low level of bone marrow Rag-1 mRNA in athymic nude mice at an age when this gene is maximally expressed in euthymic mice. Another characteristic of B cells in nude mice is their preferential rearrangement of diversity region (D)-proximal heavy-chain variable region (V(H)) genes. We demonstrated that injection of syngeneic splenic T cells into nude mice not only stimulates an increase in Rag-1 mRNA in their bone marrow B-cell precursors but also restores their random use of V(H) genes. Most interestingly, injection of supernatant medium from phytohemagglutinin- activated splenic T-cell cultures from young euthymic mice also induces both Rag-1 mRNA in bone marrow B-cell precursors and random use of V(H) genes. These findings suggest that thymic function can regulate both Rag-1 gene expression and V(H) gene use by bone marrow B-cell precursors. |
| Keywords: | controlled study; nonhuman; polymerase chain reaction; proteins; animal cell; dna recombination; animal; mice; gene expression; bone marrow; animal experiment; embryo development; mice, inbred balb c; mice, inbred c57bl; animalia; mus musculus; b-lymphocytes; stem cell; gene expression regulation; immunoglobulin heavy chain; gene rearrangement; immunoglobulin gene; immunoglobulin variable region; molecular sequence data; mice, nude; thymus; thymus gland; messenger rna; rna, messenger; hematopoietic stem cells; base sequence; aging; bone marrow cell; dna primers; t lymphocyte activation; b lymphocyte differentiation; transplantation, isogeneic; lymphocyte transfusion; phytohemagglutinin; messenger rna synthesis; female; priority journal; article; support, u.s. gov't, p.h.s. |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 91 |
| Issue: | 25 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 1994-12-06 |
| Start Page: | 11988 |
| End Page: | 11992 |
| Language: | English |
| DOI: | 10.1073/pnas.91.25.11988 |
| PROVIDER: | scopus |
| PMCID: | PMC45361 |
| PUBMED: | 7991570 |
| DOI/URL: | |
| Notes: | Export Date: 14 January 2019 -- Article -- CODEN: PNASA -- Source: Scopus |
