Mass cytometry analysis reveals attrition of naïve and anergized self-reactive non-malignant B cells in chronic lymphocytic leukemia patients.

Chronic Lymphocytic Leukemia (CLL) is characterized by the progressive accumulation of monoclonal mature B lymphocytes. Autoimmune complications are common in CLL occurring in up to a quarter of all patients during the course of the illness. Etiology of autoimmunity in CLL is unknown but it is widely admitted that the pathogenic auto-Abs do not originate from the tumoral clone but from the non-malignant B cell pool. This indicates that the developmental scheme of non-malignant B cells could also be perturbed in CLL patients. To address this question, we have designed a B cell-centered antibody panel and used time-of-flight mass cytometry to compare the residual non-malignant B cell pool of CLL patients with the peripheral B cell pool of age-matched healthy donors. We show that the non-malignant B cell compartment of the patients is characterized by profound attrition of naïve B cells and of a population of anergized autoreactive B cells, suggesting impaired B cell lymphopoeisis as well as perturbations of the B cell tolerance checkpoints.

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Copyright © 2022 Andrieu, Mondière, Jouve, Dussurgey, Malassigné, Servanton, Baseggio, Davi, Michallet and Defrance.

Déclaration de conflit d'intérêts

Author P-EJ was employed by company AltraBio SAS. Author HS was employed by company France Biotech. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.