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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1983 Sep;80(18):5734–5738. doi: 10.1073/pnas.80.18.5734

Cycling of peripheral blood and marrow lymphocytes in cyclic neutropenia.

D Engelhard, K S Landreth, N Kapoor, P W Kincade, L E De Bault, A Theodore, R A Good
PMCID: PMC384333  PMID: 6351065

Abstract

A 16-month-old male patient with cyclic neutropenia was found to have cyclic fluctuations of monocytes, lymphocytes, platelets, and eosinophils in the peripheral blood. Changes in lymphocyte counts were not obviously related to B, T, or natural killer cells. All classes of immunoglobulins were elevated throughout the cycle. Studies of the marrow morphology revealed remarkable cyclic oscillations of lymphoid as well as myeloid lineage cells. Granulocyte-macrophage progenitors (CFU-c) cycled and were virtually absent 1 wk prior to the neutropenic nadir. The cyclic changes in marrow lymphoid cell numbers were primarily due to changes in numbers of surface immunoglobulin negative (sIg-), cytoplasmic Ig+ (cIg+) pre-B cells. Pre-B cell numbers cycled from normal to extraordinarily elevated values with the same periodicity but reciprocal to the neutrophil cycle. We propose that the primary defect in cyclic neutropenia may either be a periodic failure of an early myeloid differentiation factor or a blunted response of early myeloid precursors to a common hemopoietic growth factor. This may lead to periodic fluctuations in the production or delivery of growth factors (or factor) that influence early stages of differentiation of other hemopoietic cells, including pre-B cells. The essential periodic deficiency is consequently reflected in deficient production of CFU-c accompanied by excessive production or accumulation of pre-B cells (and probably other hemopoietic precursors) in the marrow.

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Selected References

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  1. Abo T., Balch C. M. A differentiation antigen of human NK and K cells identified by a monoclonal antibody (HNK-1). J Immunol. 1981 Sep;127(3):1024–1029. [PubMed] [Google Scholar]
  2. Abo T., Cooper M. D., Balch C. M. Postnatal expansion of the natural killer and keller cell population in humans identified by the monoclonal HNK-1 antibody. J Exp Med. 1982 Jan 1;155(1):321–326. doi: 10.1084/jem.155.1.321. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Andrews R. B., Dunn C. D., Jolly J., Jones J. B., Lange R. D. Some immunological and haematological aspects of human cyclic neutropenia. Scand J Haematol. 1979 Feb;22(2):97–104. doi: 10.1111/j.1600-0609.1979.tb00409.x. [DOI] [PubMed] [Google Scholar]
  4. Angus K., Wyand D. S., Yang T. J. Impaired lymphocyte response to phytohemagglutinin in dogs affected with cyclic neutropenia. Clin Immunol Immunopathol. 1978 Sep;11(1):39–51. doi: 10.1016/0090-1229(78)90202-7. [DOI] [PubMed] [Google Scholar]
  5. Borkowsky W., Shenkman L., Rausen A. T-lymphocyte cycling in human cyclic neutropenia: effects of lithium in vitro and in vivo. Clin Immunol Immunopathol. 1982 Jun;23(3):586–592. doi: 10.1016/0090-1229(82)90321-x. [DOI] [PubMed] [Google Scholar]
  6. Burrows P. D., Kearney J. F., Lawton A. R., Cooper M. D. Pre-B cells: bone marrow persistence in anti-mu-suppressed mice, conversion to B lymphocytes, and recovery after destruction by cyclophosphamide. J Immunol. 1978 May;120(5):1526–1531. [PubMed] [Google Scholar]
  7. Day N. K., Winfield J. B., Gee T., Winchester R., Teshima H., Kunkel H. G. Evidence for immune complexes involving anti-lymphocyte antibodies associated with hypocomplementaemia in chronic lymphocytic leukaemia (CLL). Clin Exp Immunol. 1976 Nov;26(2):189–195. [PMC free article] [PubMed] [Google Scholar]
  8. Dunn C. D., Jolly J. D., Jones J. B., Lange R. D. Erythroid colony formation in vitro from the marrow of dogs with cyclic hematopoiesis: interrelationship of progenitor cells. Exp Hematol. 1978 Oct;6(9):701–708. [PubMed] [Google Scholar]
  9. Fulop G. M., Osmond D. G. Regulation of bone marrow lymphocyte production. III. Increased production of B and non-B lymphocytes after administering systemic antigens. Cell Immunol. 1983 Jan;75(1):80–90. doi: 10.1016/0008-8749(83)90307-6. [DOI] [PubMed] [Google Scholar]
  10. Gathings W. E., Lawton A. R., Cooper M. D. Immunofluorescent studies of the development of pre-B cells, B lymphocytes and immunoglobulin isotype diversity in humans. Eur J Immunol. 1977 Nov;7(11):804–810. doi: 10.1002/eji.1830071112. [DOI] [PubMed] [Google Scholar]
  11. Greenberg P. L., Schrier S. L. Granulopoiesis in neutropenic disorders. Blood. 1973 Jun;41(6):753–769. [PubMed] [Google Scholar]
  12. Guerry D., 4th, Dale D. C., Omine M., Perry S., Wolff S. M. Periodic hematopoiesis in human cyclic neutropenia. J Clin Invest. 1973 Dec;52(12):3220–3230. doi: 10.1172/JCI107522. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hoffman R. A., Kung P. C., Hansen W. P., Goldstein G. Simple and rapid measurement of human T lymphocytes and their subclasses in peripheral blood. Proc Natl Acad Sci U S A. 1980 Aug;77(8):4914–4917. doi: 10.1073/pnas.77.8.4914. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Jacobsen N., Broxmeyer H. E. Oscillations of granulocytic and megakaryocytic progenitor cell populations in cyclic neutropenia in man. Scand J Haematol. 1979 Jul;23(1):33–36. doi: 10.1111/j.1600-0609.1979.tb02850.x. [DOI] [PubMed] [Google Scholar]
  15. Jones J. B., Jolly J. D. Canine cyclic haematopoiesis: bone marrow adherent cell influence of CFU-C formation. Br J Haematol. 1982 Apr;50(4):607–617. doi: 10.1111/j.1365-2141.1982.tb01961.x. [DOI] [PubMed] [Google Scholar]
  16. Jyonouchi H., Kincade P. W., Good R. A. Immunosuppression of marrow B lymphocytes by administration of Corynebacterium parvum in mice. J Immunol. 1981 Dec;127(6):2502–2507. [PubMed] [Google Scholar]
  17. Kincade P. W. Formation of B lymphocytes in fetal and adult life. Adv Immunol. 1981;31:177–245. doi: 10.1016/s0065-2776(08)60921-9. [DOI] [PubMed] [Google Scholar]
  18. Landreth K. S., Kincade P. W., Lee G., Gathings W. E., Fu S. M. Enrichment of human marrow lymphocytes with monoclonal antibodies to murine antigens. Proc Natl Acad Sci U S A. 1982 Apr;79(7):2370–2374. doi: 10.1073/pnas.79.7.2370. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Landreth K. S., Rosse C., Clagett J. Myelogenous production and maturation of B lymphocytes in the mouse. J Immunol. 1981 Nov;127(5):2027–2034. [PubMed] [Google Scholar]
  20. Lange R. D., Crowder C. G., Cruz P., Hawkinson S. W., Lozzio C. B., Machado E., Painter P., Terry W., Jones J. B. Cyclic neutropenia. A tale of two brothers and their family. Am J Pediatr Hematol Oncol. 1981 Summer;3(2):127–133. [PubMed] [Google Scholar]
  21. Lange R. D., Jones J. B. Cyclic hematopoiesis: etiological concepts. Clinical research update. Am J Pediatr Hematol Oncol. 1982 Summer;4(2):223–229. [PubMed] [Google Scholar]
  22. Lund J. E., Padgett G. A., Ott R. L. Cyclic neutropenia in grey collie dogs. Blood. 1967 Apr;29(4):452–461. [PubMed] [Google Scholar]
  23. Owen J. J., Wright D. E., Habu S., Raff M. C., Cooper M. D. Studies on the generation of B lymphocytes in fetal liver and bone marrow. J Immunol. 1977 Jun;118(6):2067–2072. [PubMed] [Google Scholar]
  24. PAGE A. R., GOOD R. A. Studies on cyclic neutropenia; a clinical and experimental investigation. AMA J Dis Child. 1957 Dec;94(6):623–661. doi: 10.1001/archpedi.1957.04030070035006. [DOI] [PubMed] [Google Scholar]
  25. Wright D. G., Dale D. C., Fauci A. S., Wolff S. M. Human cyclic neutropenia: clinical review and long-term follow-up of patients. Medicine (Baltimore) 1981 Jan;60(1):1–13. doi: 10.1097/00005792-198101000-00001. [DOI] [PubMed] [Google Scholar]

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