Hepatitis C virus (HCV) in lymphocyte subsets and in B lymphocytes expressing rheumatoid factor cross‐reacting idiotype in type II mixed cryoglobulinaemia

The IgMk rheumatoid factors (RF) of type II mixed cryoglobulinaemia (MC) react, in 95% of cases, with MoAbs against the cross‐reactive idiotypes (CRI) Cc1 or Lc1 (corresponding to the products of the V H 1 and V H 4 genes). MC is closely associated with HCV infection, a virus which infects lymphocytes and may replicate in B cells. It has been suggested that HCV may induce clonal selection of B cells producing monoclonal IgMk RF in type II MC. To verify whether HCV is enriched in B cells, and in the subsets expressing Cc1 and Lc1 CRI, we studied peripheral blood lymphocytes from eight patients with MC and HCV RNA‐positive sera. Seven patients had RF reacting with anti‐Cc1, the other with anti‐Lc1 CRI. Total lymphocytes, T cells, B cells, and Cc1 + or Lc1 + , Cc1 − or Lc1 − B cells were purified using MoAb‐coated magnetic beads. Lymphocyte subsets were then diluted to give a range of 1 × 10 6 −1 × 10 3 cells and tested for HCV RNA by reverse transcriptase‐polymerase chain reaction. HCV was found exclusively in B cells in seven out of eight patients. In three patients HCV was enriched in the Cc1 + cells. In one of these patients, HCV was found exclusively in Cc1 + cells, with Cc1 − cells being HCV − . The data indicate that B cells from type II MC patients are almost constantly infected by HCV. In selected cases, B cell subsets expressing IgMk RF CRI are the prevalent cell type infected by HCV. Our data suggest HCV involvement in B cell dysregulation leading to cryoprecipitable IgMk RF production.