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) re act, 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). M C is closely associated with HCV infection, a virus which infects lymphocyt es 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 Cc 1 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 x 10(6)-1 x 10(3) cells and tested for HCV RNA by reverse transcriptase-pol ymerase chain reaction. HCV was found exclusively in B cells in seven out o f eight patients. In three patients HCV was enriched in the Cc1(+) cells. I n one of these patients, HCV was found exclusively in Cc1(+) cells, with Cc 1(-) cells being HCV-. The data indicate that B cells from type II MC patie nts are almost constantly infected by HCV. In selected cases, B cell subset s expressing IgMk RF CRI are the prevalent cell type infected by HCV. Our d ata suggest HCV involvement in B cell dysregulation leading to cryoprecipit able IgMk RF production.