Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Abnormal NK Cell Lymphocytosis Detected after Splenectomy: Association with Repeated Infections, Relapsing Neutropenia, and Persistent Polyclonal B-Cell Proliferation

  • 69 Accesses

  • 3 Citations


We report the case of a boy with hereditary spherocytosis who presented with mild microcytic hypochromic anemia and recurrent leg ulcers that had been present since childhood. Chronic natural killer (NK) cell and B-cell lymphocytosis was detected 1 year after therapeutic splenectomy during investigation of recurrent episodes of neutropenia and persistent lymphocytosis. NK cells proved to be abnormal at immunophenotyping studies, and B-cells were polyclonal and displayed a normal immunophenotype. Genotypic analysis of T-cell receptor (TCR)-β and TCR-γ genes showed a germ-line pattern. The clinical course of this patient was characterized by multiple pulmonary infections and amygdalitis. We discuss the potential roles of persistent immune stimulation due to chronic hemolysis and severe leg ulcers and of splenectomy in the origin of NK cell lymphocytosis and the relationship between NK cells and recurrent infections, relapsing neutropenia, and polyclonal B-cell response.Int J Hematol. 2002;75:484–488.

This is a preview of subscription content, log in to check access.


  1. 1.

    Hassoun H, Palek J. Hereditary spherocytosis: a review of the clinical and molecular aspects of the disease.Blood Rev. 1996;10: 129–147.

  2. 2.

    Granjo E, Moreira I, Santos Silva A, et al. Lymphocyte populations in hereditary spherocytosis pre and post splenectomy and under oxidative stress.Mol Biol Hematopoiesis. 1999;6:347–352.

  3. 3.

    Conti JA, Howard LM. Hereditary spherocytosis and haematological malignancy.N J Med. 1994;91:95–97.

  4. 4.

    Trinchieri G. Natural killer cells wear different hats: effector cells of innate resistance and regulatory cells of adaptative immunity and of haematopoiesis.Semin Immunol. 1995;7:83–88.

  5. 5.

    Lima M, Teixeira MA, Queirós ML, et al. Immunophenotypic characterization of normal blood CD56+lo versus CD56+hi NK- cell subsets and its impact on the understanding of their tissue distribution and functional properties.Blood Cells Mol Dis. 2001;27: 731–743.

  6. 6.

    Jaffe ES. Classification of natural killer (NK) cell and NK-like T cell malignancies.Blood. 1996;87:1207–1210.

  7. 7.

    Tefferi A. Chronic natural killer cell lymphocytosis.Leuk Lymphoma. 1996;20:245–248.

  8. 8.

    Rabbani GR, Phyliky RL, Tefferi A. A long-term study of patients with chronic natural killer cell lymphocytosis.Br J Haematol. 1999; 106:960–966.

  9. 9.

    Lima M, Almeida J, Santos A, et al. Immunophenotypic analysis of the TCR-Vγ repertoire in 98 persistent expansions of CD3+/ TCRαβ+ large granular lymphocytes: utility in assessing clonality and insights into the pathogenesis of the disease.Am J Pathol. 2001;159:1861–1868.

  10. 10.

    Scott CS, Richards SJ, Sivakumaran M, et al.Transient and persistent expansions of large granular lymphocytes (LGL) and NK associated (NKa) cells: the Yorkshire Leukaemia Group Study.Br J Haematol. 1993;83:505–517.

  11. 11.

    Richards SJ, Short M, Scott CS. Clonal CD3+CD8+ large granular lymphocyte (LGL)/NK-associated (NKa) expansions: primary malignancies or secondary reactive phenomena?Leuk Lymphoma. 1985;17:303–311.

  12. 12.

    Kelemen E, Gergely P, Lehockzy D, et al. Permanent large granular lymphocytosis in the blood of splenectomized individuals without concomitant increase of in vitro natural killer cell cytotoxicity.Clin Exp Immunol. 1986;63:696–702.

  13. 13.

    Garcia-Suarez J, Prieto A, Reyes E, et al. Persistent lymphocytosis of NK cells in autoimmune thrombocytopenic purpura (ATP) patients after splenectomy.Br J Haematol. 1995;89: 653–655.

  14. 14.

    Orloff DG, Ra CS, Frank SJ, et al. Family of disulphide-linked dimers containing the zeta and the eta chains of the T-cell receptor and the gamma chain of the Fc receptor.Nature. 1990;347: 189–191.

  15. 15.

    Phillips JH, Hori T, Nagler A, et al. Ontogeny of human natural killer (NK) cells: fetal NK cells mediate cytolytic function and express cytoplasmic CD3 epsilon and delta proteins.J Exp Med. 1992;175:1055–1066.

  16. 16.

    Bassan R, Pronesti M, Buzzetti M, et al. Autoimmunity and B-cell dysfunction in chronic proliferative disorders of large granular lymphocytes/natural killer cells.Cancer. 1989;63:90–95.

  17. 17.

    Procopio ADG, Allavena P, Ortaldo JK. Non-cytotoxic functions of natural killer cells: large granular lymphocytes produce a B-cell growth factor (BCGF).J Immunol. 1985;135:3264–3271.

  18. 18.

    Yuan D, Kohn CY, Wilder JA. Interactions between B lymphocytes and NK cells.FASEB J. 1994;8:1012–1018.

Download references

Author information

Correspondence to Elisa Granjo or Margarida Lima or Manuela Fraga or Filipe Santos or Conceição Magalhães or Maria Luís Queirós or Ilidia Moreira or Sandra Rocha or Alice Santos Silva or Irene Rebelo or Alexandre Quintanilha or Maria Letícia Ribeiro or Jorge Candeias or Alberto Orfão.

About this article

Cite this article

Granjo, E., Lima, M., Fraga, M. et al. Abnormal NK Cell Lymphocytosis Detected after Splenectomy: Association with Repeated Infections, Relapsing Neutropenia, and Persistent Polyclonal B-Cell Proliferation. Int J Hematol 75, 484–488 (2002). https://doi.org/10.1007/BF02982110

Download citation

Key words

  • NK cells
  • Neutropenia
  • B-cells
  • Spherocytosis
  • Splenectomy