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A good correlation between ZAP70 expression in CLL cells and the occurrence of autoimmune phenomena has been reported. Yet, the great majority of CLL\u2010associated 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\u2010 nonmalignant B cells from CLL patients expresses ZAP70 compared with CD5\u2010 B cells from healthy subjects. This ZAP70 expression in normal B cells from CLL patients was also evidenced by the detection of <jats:italic>ZAP70<\/jats:italic> mRNA at single\u2010cell level with polyclonal Ig heavy\u2010 and light\u2010chain gene transcripts. ZAP70+ normal B cells belong to various B\u2010cell subsets and their presence in the na\u00efve B\u2010cell subset suggests that ZAP70 expression may occur during early B\u2010cell 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\u2010platelet reactivity. These results provide a better understanding of the implication of ZAP70 in CLL leukemogenesis and the mechanisms of autoimmune complications of CLL.<\/jats:p>","DOI":"10.1002\/ajh.27137","type":"journal-article","created":{"date-parts":[[2023,10,19]],"date-time":"2023-10-19T07:06:44Z","timestamp":1697699204000},"page":"48-56","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Normal B cells express <scp>ZAP70<\/scp> in chronic lymphocytic leukemia: A link between autoimmunity and lymphoproliferation?"],"prefix":"10.1002","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6525-0348","authenticated-orcid":false,"given":"Dana","family":"Ghergus","sequence":"first","affiliation":[{"name":"Strasbourg University  Strasbourg France"},{"name":"Department of Clinical Hematology Hospices Civils de Lyon  Lyon 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