Persistence of a Large Population of Exhausted Monoclonal B cells in Mixed Cryoglobuliemia After the Eradication of Hepatitis C Virus Infection

Purpose Functionally exhausted and mostly autoreactive B-cells with a peculiar CD21lowCD11c+ phenotype accumulate in several human immunological disorders including common variable immunodeficiency, HIV infection and rheumatoid arthritis. In HCV-associated mixed cryoglobulinemia (MC) there is accumulation of exhausted clonal B cells expressing a VH1-69-encoded cross-reactive idiotype; these cells are phenotypically heterogeneous, displaying either a CD21lowCD11c+ or a marginal zone (MZ)-like (IgM+CD27+CD21+CD11c-) phenotype. Irrespective of their phenotype, VH1-69+ B-cells are unresponsive to the stimulation of Toll-like receptor 9 (TLR9). We investigated the fate of these cells after the eradication of HCV.