Expansion of innate CD5pos B cells expressing high levels of CD81 in hepatitis C virus infected liver.
OBJECTIVE
Association of hepatitis C virus (HCV) with increased autoantibodies, mixed cryoglobulinaemia, non-Hodgkin's B-cell lymphoma and increased peripheral innate (CD5(pos)) B cells suggests a role for B-lymphocytes in the pathogenesis of HCV-infection.


METHODS
Flow cytometry was used to estimate CD5(pos) B cell levels and CD81 co-expression in chronic HCV infection. Viral load was assessed using PCR.


RESULTS
We demonstrate expansion of innate B cells in HCV-infected liver from patients with fibrosis score less than stage II (39%, % of total B cells, P=0.002) and end stage HCV cirrhosis (20%, P<0.05) compared with normal liver (8%). Expression of CD81, a signal transducing molecule and putative HCV receptor, was significantly increased on peripheral blood CD5(pos) B cells compared with conventional B cells (P=0.0001). Higher levels of CD81 on CD5(pos) B cells were more dramatic in the liver of HCV-infected individuals. However, no significant difference was observed in the viral load of CD5(pos)CD81(High) B cells and CD5(neg)CD81(Low) B cells.


CONCLUSIONS
Increased expression of CD81 on innate B cells, a population that is expanded in the livers and peripheral blood of chronic HCV-infected patients, suggests a role in viral specific activation and clonal proliferation in chronic HCV infection.
Curry
Michael P
MP
The Liver Unit, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland.
Golden-Mason
Lucy
L
Doherty
Derek G
DG
Deignan
Tina
T
Norris
Suzanne
S
Duffy
Margaret
M
Nolan
Niamh
N
Hall
William
W
Hegarty
John E
JE
O'Farrelly
Cliona
C
D000328:Adult; D015703:Antigens, CD / Q000378:metabolism*; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D018956:CD5 Antigens / Q000378:metabolism*; D005260:Female; D016174:Hepacivirus / Q000254:growth & development / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000276:immunology* / Q000473:pathology; D006801:Humans; D008099:Liver / Q000276:immunology / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D012367:RNA, Viral / Q000032:analysis; D060225:Tetraspanin 28; D019562:Viral Load
D015703:Antigens, CD; D018956:CD5 Antigens; C554798:CD81 protein, human; D008565:Membrane Proteins; D012367:RNA, Viral; D060225:Tetraspanin 28