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 VH1 and VH4 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 x 106-1 x 103 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.
Fornasieri
A
A
Division of Nephrology and Immunohaematology, San Carlo Borromeo Hospital, and Institute of Virology, University of Milano, Milano, Italy. a.fornasieri@oscb.sined.net
Bernasconi
P
P
Ribero
M L
ML
Sinico
R A
RA
Fasola
M
M
Zhou
J
J
Portera
G
G
Tagger
A
A
Gibelli
A
A
D'amico
G
G
D000328:Adult; D000368:Aged; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D001324:Autoantigens / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology / Q000821:virology*; D003429:Cross Reactions; D003449:Cryoglobulinemia / Q000276:immunology / Q000821:virology*; D003450:Cryoglobulins / Q000032:analysis; D005260:Female; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology; D007136:Immunoglobulins / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology / Q000821:virology; D016131:Lymphocyte Subsets / Q000276:immunology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000032:analysis; D012217:Rheumatoid Factor / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology
D000888:Antibodies, Anti-Idiotypic; D001324:Autoantigens; D003450:Cryoglobulins; C014609:IgK; D007075:Immunoglobulin M; D007136:Immunoglobulins; D012367:RNA, Viral; C077285:liver cytosol antigen type 1, human; D012217:Rheumatoid Factor