HEPATITIS-C VIRUS-INFECTION AND CLONAL B-CELL EXPANSION

The striking association between hepatitis C virus (HCV) infection and the so-called ''essential'' mixed cryoglobulinemia (MC) has led to th e hypothesis that HCV plays a major role in the production of cryoglob ulins. Analysis of soluble and cryoprecipitable immune complexes shows that the hepatitis C virion is bound to IgM bearing the WA cross-idio type (Xld), The production of WA Xld IgM seems to be the result of chr onic stimulation by HCV of a population of WA Xld+ CD5+ B cells. It is possible that the reactivity of WA XldIgM does not initially include rheumatoid factor (RF) activity, which may be acquired secondarily fro m mutational events accompanying a probably T-cell independent B cell proliferation. Type II MC is a benign proliferation that progresses to malignancy in a minority of patients. This is consistent with the con cept that malignancy progression involves the accumulation of multiple mutations of proto-oncogenes and tumor suppressor genes that are faci litated by chronic antigenic stimulation. The recent demonstration of HCV in hyperplastic reactive lymphoadenopathy and in the neoplastic ly mph nodes of patients with MC strengthens the putative role played by HCV in lymphomagenesis. A fuller understanding of the virus-related me chanisms of lymphoproliferation in MC patients would contribute signif icantly to the development of therapeutic strategies.