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. 1993 Dec;80(4):587–592.

Chronic elevation of plasma corticosterone causes reductions in the number of cycling cells of the B lineage in murine bone marrow and induces apoptosis.

B A Garvy 1, L E King 1, W G Telford 1, L A Morford 1, P J Fraker 1
PMCID: PMC1422241  PMID: 8307608

Abstract

Steroid-containing implants were used to ascertain the effects of chronic elevation of physiological levels of plasma corticosterone (CS) (30-100 micrograms/dl) on lymphopoietic processes in the bone marrow of the mouse. Phenotypic analysis of bone marrow B-lineage lymphocytes using flow cytometry (FACS) indicated a 50% decrease in bone marrow Ig+ cells, and a 70-80% decrease in B220+ cells had occurred 3 days after exposure to steroid. By day 5, the B220+ Ig- precursor B cells in the marrow of mice exposed to CS were nearly depleted, with many of the remaining B cells being B220bright IgM+IgDbright. To determine if the depletion of B cells was due to disruption in cell cycling and/or induction of apoptosis, phenotype-gated FACS cell cycle analysis was utilized. The proportion of B220+ cells in the S phase of the cell cycle declined 75% after 24 hr exposure to CS. A few hours after CS implantation, the appearance of a small but distinct population of B220+ and IgM+ cells in the 'hypodiploid' region of the cell cycle was also noted, which was previously termed the Ao region and corresponded to cells undergoing apoptosis. Thus, the chronic presence of modestly elevated levels of plasma CS analogous to that produced during malnutrition, stress and trauma caused rapid depletion of developing B-lineage cells in the marrow by reducing the number of cycling precursor B cells and inducing apoptosis.

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Selected References

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  1. Alleyne G. A., Young V. H. Adrenocortical function in children with severe protein-calorie malnutrition. Clin Sci. 1967 Aug;33(1):189–200. [PubMed] [Google Scholar]
  2. Benhamou L. E., Cazenave P. A., Sarthou P. Anti-immunoglobulins induce death by apoptosis in WEHI-231 B lymphoma cells. Eur J Immunol. 1990 Jun;20(6):1405–1407. doi: 10.1002/eji.1830200630. [DOI] [PubMed] [Google Scholar]
  3. Compton M. M., Cidlowski J. A. Rapid in vivo effects of glucocorticoids on the integrity of rat lymphocyte genomic deoxyribonucleic acid. Endocrinology. 1986 Jan;118(1):38–45. doi: 10.1210/endo-118-1-38. [DOI] [PubMed] [Google Scholar]
  4. DePasquale-Jardieu P., Fraker P. J. Further characterization of the role of corticosterone in the loss of humoral immunity in zinc-deficient A/J mice as determined by adrenalectomy. J Immunol. 1980 Jun;124(6):2650–2655. [PubMed] [Google Scholar]
  5. Duvall E., Wyllie A. H., Morris R. G. Macrophage recognition of cells undergoing programmed cell death (apoptosis). Immunology. 1985 Oct;56(2):351–358. [PMC free article] [PubMed] [Google Scholar]
  6. Era T., Ogawa M., Nishikawa S., Okamoto M., Honjo T., Akagi K., Miyazaki J., Yamamura K. Differentiation of growth signal requirement of B lymphocyte precursor is directed by expression of immunoglobulin. EMBO J. 1991 Feb;10(2):337–342. doi: 10.1002/j.1460-2075.1991.tb07954.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Garvy B. A., Fraker P. J. Suppression of the antigenic response of murine bone marrow B cells by physiological concentrations of glucocorticoids. Immunology. 1991 Nov;74(3):519–523. [PMC free article] [PubMed] [Google Scholar]
  8. Garvy B. A., Telford W. G., King L. E., Fraker P. J. Glucocorticoids and irradiation-induced apoptosis in normal murine bone marrow B-lineage lymphocytes as determined by flow cytometry. Immunology. 1993 Jun;79(2):270–277. [PMC free article] [PubMed] [Google Scholar]
  9. Gu H., Tarlinton D., Müller W., Rajewsky K., Förster I. Most peripheral B cells in mice are ligand selected. J Exp Med. 1991 Jun 1;173(6):1357–1371. doi: 10.1084/jem.173.6.1357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Harmon J. M., Norman M. R., Fowlkes B. J., Thompson E. B. Dexamethasone induces irreversible G1 arrest and death of a human lymphoid cell line. J Cell Physiol. 1979 Feb;98(2):267–278. doi: 10.1002/jcp.1040980203. [DOI] [PubMed] [Google Scholar]
  11. Kagan R. J., Bratescu A., Jonasson O., Matsuda T., Teodorescu M. The relationship between the percentage of circulating B cells, corticosteroid levels, and other immunologic parameters in thermally injured patients. J Trauma. 1989 Feb;29(2):208–213. doi: 10.1097/00005373-198902000-00010. [DOI] [PubMed] [Google Scholar]
  12. Kincade P. W., Lee G., Pietrangeli C. E., Hayashi S., Gimble J. M. Cells and molecules that regulate B lymphopoiesis in bone marrow. Annu Rev Immunol. 1989;7:111–143. doi: 10.1146/annurev.iy.07.040189.000551. [DOI] [PubMed] [Google Scholar]
  13. Ku G., Witte O. N. Corticosteroid-resistant bone marrow-derived B lymphocyte progenitor for long term in vitro cultures. J Immunol. 1986 Nov 1;137(9):2802–2807. [PubMed] [Google Scholar]
  14. Opstelten D., Osmond D. G. Pre-B cells in mouse bone marrow: immunofluorescence stathmokinetic studies of the proliferation of cytoplasmic mu-chain-bearing cells in normal mice. J Immunol. 1983 Dec;131(6):2635–2640. [PubMed] [Google Scholar]
  15. Rodriguez-Tarduchy G., Collins M., López-Rivas A. Regulation of apoptosis in interleukin-3-dependent hemopoietic cells by interleukin-3 and calcium ionophores. EMBO J. 1990 Sep;9(9):2997–3002. doi: 10.1002/j.1460-2075.1990.tb07492.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Rolink A., Kudo A., Karasuyama H., Kikuchi Y., Melchers F. Long-term proliferating early pre B cell lines and clones with the potential to develop to surface Ig-positive, mitogen reactive B cells in vitro and in vivo. EMBO J. 1991 Feb;10(2):327–336. doi: 10.1002/j.1460-2075.1991.tb07953.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Sabbele N. R., Van Oudenaren A., Hooijkaas H., Benner R. The effect of corticosteroids upon murine B cells in vivo and in vitro as determined in the LPS-culture system. Immunology. 1987 Oct;62(2):285–290. [PMC free article] [PubMed] [Google Scholar]
  18. Savill J., Dransfield I., Hogg N., Haslett C. Vitronectin receptor-mediated phagocytosis of cells undergoing apoptosis. Nature. 1990 Jan 11;343(6254):170–173. doi: 10.1038/343170a0. [DOI] [PubMed] [Google Scholar]
  19. Spackman D. H., Riley V. Corticosterone concentrations in the mouse. Science. 1978 Apr 7;200(4337):87–87. doi: 10.1126/science.635580. [DOI] [PubMed] [Google Scholar]
  20. Telford W. G., King L. E., Fraker P. J. Evaluation of glucocorticoid-induced DNA fragmentation in mouse thymocytes by flow cytometry. Cell Prolif. 1991 Sep;24(5):447–459. doi: 10.1111/j.1365-2184.1991.tb01173.x. [DOI] [PubMed] [Google Scholar]
  21. Vines R. L., Coleman M. S., Hutton J. J. Reappearance of terminal deoxynucleotidyl transferase containing cells in rat bone marrow following corticosteroid administration. Blood. 1980 Sep;56(3):501–509. [PubMed] [Google Scholar]
  22. Weissman I. L. Thymus cell maturation. Studies on the origin of cortisone-resistant thymic lymphocytes. J Exp Med. 1973 Feb 1;137(2):504–510. doi: 10.1084/jem.137.2.504. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Wyllie A. H. Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation. Nature. 1980 Apr 10;284(5756):555–556. doi: 10.1038/284555a0. [DOI] [PubMed] [Google Scholar]

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