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.