Normal B cells express ZAP70 in chronic lymphocytic leukemia: A link between autoimmunity and lymphoproliferation?

Autor: Ghergus D; Strasbourg University, Strasbourg, France.; Department of Clinical Hematology, Hospices Civils de Lyon, Lyon, France., Martin M; Strasbourg University, Strasbourg, France.; Department of Clinical Immunology and Internal Medicine, Tertiary Center for Primary Immunodeficiency, National Reference Center for Systemic Autoimmune Diseases (CNR RESO), Strasbourg University Hospital, Strasbourg, France.; Department of Internal Medicine, Poitiers University Hospital, Poitiers, France., Knapp AM; Strasbourg University, Strasbourg, France., Delmotte F; Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA., Joublin-Delavat A; Strasbourg University, Strasbourg, France., Jung S; Strasbourg University, Strasbourg, France.; Faculty of Dentistry, Strasbourg University, Strasbourg, France., Schickel JN; Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA., Mendel I; French Blood Institute of Strasbourg, Strasbourg, France., Dupuis A; French Blood Institute of Strasbourg, Strasbourg, France., Drénou B; Department of Hematology, Groupe Hospitalier de la Région Mulhouse Sud Alsace, Mulhouse, France., Ghesquières H; Department of Clinical Hematology, Hospices Civils de Lyon, Lyon, France., Salles G; Department of Clinical Hematology, Hospices Civils de Lyon, Lyon, France., Baseggio L; Laboratory of Hematology, Hospices Civils de Lyon, Lyon, France., Herbrecht R; Department of Hematology, Institut de Cancérologie Strasbourg Europe (ICANS), Strasbourg, France.; Strasbourg University, IINSERM UMR-S1113/IRFAC, Strasbourg, France., Korganow AS; Strasbourg University, Strasbourg, France.; Department of Clinical Immunology and Internal Medicine, Tertiary Center for Primary Immunodeficiency, National Reference Center for Systemic Autoimmune Diseases (CNR RESO), Strasbourg University Hospital, Strasbourg, France., Vallat L; Department of Molecular Genetics of Cancer, Strasbourg University Hospital and INSERM UMR-S1113, Strasbourg, France., Soulas-Sprauel P; Strasbourg University, Strasbourg, France.; Faculty of Pharmacy, Strasbourg University, Strasbourg, France., Meffre E; Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA., Martin T; Strasbourg University, Strasbourg, France.; Department of Clinical Immunology and Internal Medicine, Tertiary Center for Primary Immunodeficiency, National Reference Center for Systemic Autoimmune Diseases (CNR RESO), Strasbourg University Hospital, Strasbourg, France.
Jazyk: angličtina
Zdroj: American journal of hematology [Am J Hematol] 2024 Jan; Vol. 99 (1), pp. 48-56. Date of Electronic Publication: 2023 Oct 19.
DOI: 10.1002/ajh.27137
Abstrakt: ZAP70 has a prognostic value in chronic lymphocytic leukemia (CLL), through altered B-cell receptor signaling, which is important in CLL pathogenesis. A good correlation between ZAP70 expression in CLL cells and the occurrence of autoimmune phenomena has been reported. Yet, the great majority of CLL-associated autoimmune cytopenia is due to polyclonal immunoglobulin (Ig) G synthesized by nonmalignant B cells, and this phenomenon is poorly understood. Here, we show, using flow cytometry, that a substantial percentage of CD5- nonmalignant B cells from CLL patients expresses ZAP70 compared with CD5- B cells from healthy subjects. This ZAP70 expression in normal B cells from CLL patients was also evidenced by the detection of ZAP70 mRNA at single-cell level with polyclonal Ig heavy- and light-chain gene transcripts. ZAP70+ normal B cells belong to various B-cell subsets and their presence in the naïve B-cell subset suggests that ZAP70 expression may occur during early B-cell development in CLL patients and potentially before malignant transformation. The presence of ZAP70+ normal B cells is associated with autoimmune cytopenia in CLL patients in our cohort of patients, and recombinant antibodies produced from these ZAP70+ nonmalignant B cells were frequently autoreactive including anti-platelet reactivity. These results provide a better understanding of the implication of ZAP70 in CLL leukemogenesis and the mechanisms of autoimmune complications of CLL.
(© 2023 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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