B-cell lymphomagenesis and human autoimmune models

The concept that B-cell lymphomagenesis represents a multistep process is widely accepted. Pathogenetic events should be better defined both in early and late stages of lymphoproliferation. In the past few years, novel study approaches have been focused on understanding the mechanisms of lymphomagenesis. In particular, immune stimulation by infectious agents or autoantigens, T-cell help, altered immunocompetence, and local cytokine networks seem to be crucial in favouring B-cell expansions. In turn, actively proliferating B cells are at higher risk of undergoing genetic alterations that make the clone capable of fully autonomous growth, i.e., fully neoplastic. Peculiar human autoimmune diseases predisposing to B-cell lymphoma represent relevant models to characterize and dissect the temporal sequence of the different lyphomagenetic events. The present review, particularly, focuses on Sjoegren's syndrome, and on recent findings regarding the putative role of hepatitis C virus in B-cell lymphoproliferation. The biologic and clinical implications may be of major relevance for other B-cell disorders characterized by higher prevalence and morbidity.